LL-37 Cathelicidin: Antimicrobial Mechanism and Immune Signaling

Research use only. LL-37 is supplied as a research-grade reference compound for laboratory use only. It is not for human or veterinary use, and nothing on this page describes a route of administration or a quantity to use.

LL-37 is the only cathelicidin-derived antimicrobial peptide found in humans. It is a 37-residue, amphipathic, alpha-helical peptide released from the C-terminus of the hCAP18 precursor protein, which is encoded by the CAMP gene. In the published literature it is studied for direct membrane activity against bacteria and fungi, for binding and neutralizing bacterial lipopolysaccharide, and for signaling roles in the innate immune response.

This page covers what LL-37 is chemically, how the precursor is processed, the mechanisms described in the literature, and how identity and purity are verified on a certificate of analysis. Research quantities and experimental design are defined in the methodology of each cited study and are not restated here.

What Is LL-37?

LL-37 is a cationic host-defense peptide of 37 amino acids, named for the two leucine residues at its N-terminus and its length. It is the single member of the cathelicidin family expressed in humans, in contrast to species such as cattle and pigs that express several. The peptide is produced by neutrophils, epithelial cells at barrier surfaces, and several other cell types, and it is released by proteolytic cleavage from a larger stored precursor rather than synthesized in its mature form.

Its two structural features drive most of the published research. It carries a strong net positive charge, which favors association with the anionic surfaces characteristic of bacterial membranes and with lipopolysaccharide. It also folds into an amphipathic alpha helix in membrane-mimetic and anionic environments, separating hydrophobic and charged faces along the helix, which is the arrangement most peptide membrane-interaction models depend on.

Sequence, Structure and Physical Properties

The mature peptide sequence is LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES. Its average molecular weight is approximately 4493 Da and its net charge at physiological pH is approximately +6, arising from a high proportion of lysine and arginine residues against a small number of acidic residues.

Property	Value	How it is confirmed
Length	37 amino acid residues	Sequence confirmation by mass spectrometry or Edman degradation
Sequence	LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES	Peptide mapping or full sequence confirmation
Average molecular weight	Approximately 4493 Da	Mass spectrometry, reported on the COA
Net charge at pH 7.4	Approximately +6	Calculated from sequence composition
Precursor	hCAP18, an 18 kDa protein	Not applicable to the supplied reference material
Secondary structure	Amphipathic alpha helix in membrane-mimetic and anionic environments; largely unstructured in dilute aqueous buffer	Circular dichroism in the published literature

The conformational behavior matters when interpreting published work. LL-37 is substantially unstructured in dilute aqueous solution and adopts its helical fold on contact with anionic surfaces, membranes and certain buffer conditions. Studies reporting structural or aggregation behavior therefore specify the solution environment, and results are not directly comparable across different conditions. Recent membrane work has also described self-assembled multi-helix arrangements at interfaces rather than a single uniform binding mode (Langmuir, 2025; PMID 41263761). The backbone constraints behind that helical fold are covered in how peptide backbone geometry shapes helical structure.

The Cathelicidin Family and hCAP18 Processing

Cathelicidins are defined by a conserved N-terminal cathelin domain attached to a variable C-terminal antimicrobial peptide. In humans the single family member is the 18 kDa precursor hCAP18, the product of the CAMP gene. The cathelin domain holds the antimicrobial portion inactive during storage; the mature peptide is generated when the precursor is cleaved, and in neutrophils that cleavage is attributed to proteinase 3.

This explains why the literature uses several names for closely related things. Cathelicidin refers to the family and, in human work, usually to the gene product as a whole. CAMP is the gene. hCAP18 is the stored precursor protein. LL-37 is the mature cleaved peptide, and it is the form supplied as a reference compound. Expression studies frequently report hCAP18 rather than LL-37 because they measure the precursor, and CAMP transcription has been described as responsive to vitamin D signaling through a response element in the gene promoter (Biochem Biophys Res Commun, 2024; PMID 38642493). Molecular identity data for the mature peptide is set out in the LL-37 chemical reference data, and the LL-37 encyclopedia entry gives the short reference view.

Term	What it refers to
Cathelicidin	The peptide family, defined by the conserved cathelin domain. Humans express one member.
CAMP	The gene encoding the human cathelicidin precursor.
hCAP18	The 18 kDa stored precursor protein, held in an inactive form by the cathelin domain.
LL-37	The mature 37-residue peptide released by proteolytic cleavage of hCAP18. This is the reference compound.
Carbamylated LL-37	A post-translationally modified form described in the literature with altered activity (Innate Immun, 2016; PMID 26878866).

Research Focus: Mechanisms Described in the Literature

Published work on LL-37 clusters into direct antimicrobial activity, endotoxin binding, and immune signaling. The table below summarizes the mechanisms as they are described in the cited literature. Each row states the model system, because findings from cell-free membrane systems, cultured cells and animal models are not interchangeable. For a second short cationic peptide studied on the immune-signaling side, see KPV tripeptide and NF-kB signaling.

Mechanism	Model system in the cited work	What the literature describes	Reference
Membrane perturbation	Model lipid systems and bacterial membranes	Association of the cationic helix with anionic membrane surfaces, followed by disruption of bilayer integrity. Carpet-type and pore-type models are both discussed.	Biochim Biophys Acta, 2010; PMID 20036634
Lipopolysaccharide binding	Cell-free and cell-based systems	Direct binding to LPS with reduction of downstream signaling readouts, described as neutralization in the source literature.	Ann Agric Environ Med, 2007; PMID 17655171
LPS handling in immune cells	Cultured human cells	Modulation of LPS uptake and presentation in host cells rather than binding alone.	J Immunol, 2016; PMID 26729811
Chemotactic signaling	Cultured cells	Chemotactic responses in mast cells, part of the wider signaling literature on the peptide.	Immunology, 2002; PMID 11972628
Biofilm-associated activity	In vitro biofilm systems	Activity against biofilm formation and established biofilms, reviewed across multiple organisms.	World J Microbiol Biotechnol, 2023; PMID 36781570
Antifungal activity	In vitro fungal systems	Activity against fungal targets, reviewed with the current limits of the evidence.	World J Microbiol Biotechnol, 2023; PMID 38057654

Two qualifications apply across this literature. Activity in model membrane systems is strongly dependent on lipid composition, ionic strength and peptide concentration, so results are reported against the specific system used. And salt sensitivity is a recurring theme: the electrostatic association that drives membrane binding is attenuated at higher ionic strength, which is why in vitro conditions are specified in careful studies.

Chemical Identity and Verification

For a reference compound, identity and purity documentation is the part of the record that can be checked. A certificate of analysis for LL-37 should establish two separate things: that the material is the intended molecule, and how much of the sample is that molecule.

• Identity by mass spectrometry, with the observed mass compared against the calculated mass for the sequence.
• Sequence confirmation, by peptide mapping or direct sequencing, where the certificate reports it.
• Purity by reversed-phase HPLC, reported with the method conditions rather than as a bare number.
• Water content, which affects how much of the labeled mass is peptide.
• Counter-ion identity and content, commonly trifluoroacetate or acetate from the purification process.

A purity figure without its method is not interpretable, and a figure quoted from one lot does not describe another. Purity on this page always refers to the certificate for the specific lot supplied. Reading a peptide certificate of analysis sets out each of these determinations in detail, and our published lab reports hold the certificates themselves.

Storage and Handling of Sealed Material

Guidance below applies to the sealed vial as supplied. LL-37 is provided as a lyophilized powder in lyophilized research vials, a form chosen because removing water suppresses the hydrolysis and aggregation pathways that limit stability in solution.

• Store the sealed vial frozen, at -20 degrees Celsius or colder, in line with general practice for lyophilized peptides.
• Shield from light.
• Avoid repeated freeze-thaw cycling of the container.
• Allow the sealed vial to reach room temperature before opening, so that atmospheric moisture does not condense onto cold powder.

Stability duration for any given lot is documented on its certificate of analysis rather than stated as a general figure. Reconstitution means returning a lyophilized compound to solution; the solvent system, concentration and handling for a given experiment are defined by the published methodology of the study being followed and by the receiving laboratory’s own validated procedures. Related compounds are indexed in the peptide reference library.

Frequently Asked Questions

What is LL-37?

LL-37 is the only cathelicidin-derived antimicrobial peptide expressed in humans. It is a 37-residue cationic peptide released from the hCAP18 precursor protein, encoded by the CAMP gene, and it is studied for membrane activity against microorganisms, for lipopolysaccharide binding, and for signaling roles in innate immunity.

What is the LL-37 amino acid sequence?

The mature LL-37 sequence is LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES, a 37-residue peptide with an average molecular weight of approximately 4493 Da. The sequence is confirmed analytically by mass spectrometry and, where reported, by peptide mapping. Confirm the value against the certificate of analysis for the specific lot.

How is LL-37 different from cathelicidin?

Cathelicidin names the peptide family, defined by a conserved cathelin domain. Humans express a single family member, stored as the precursor protein hCAP18 and encoded by the CAMP gene. LL-37 is the mature peptide released when that precursor is cleaved, so cathelicidin describes the family and the gene product while LL-37 describes the active fragment.

Why does LL-37 carry a positive charge?

LL-37 contains a high proportion of lysine and arginine residues against few acidic residues, giving a net charge of approximately +6 at physiological pH. That charge favors association with anionic surfaces, which is the property most membrane-interaction studies are built around.

How is LL-37 purity verified?

Purity for a research peptide is determined by reversed-phase HPLC and reported alongside the method conditions on the certificate of analysis for the lot. Identity is established separately by mass spectrometry. A purity figure only describes the lot it was measured on.

Does LL-37 fold into a helix in solution?

LL-37 is largely unstructured in dilute aqueous buffer and adopts an amphipathic alpha-helical conformation on contact with anionic surfaces and membrane-mimetic environments. Structural results in the literature are therefore reported against the specific solution conditions used.

References

1. Soman D, P J, Cm M, Radhakrishnan R. LL-37 antimicrobial peptide: Molecular characterisation and its role in oral health and disease-A narrative review. Arch Oral Biol. 2026;183:106516. PMID 41544412.
2. Mitra A, Paul S. Membrane Interaction and Embedding of a Self-Assembled 4-Helix Bundle from the Antimicrobial hLL-37(17-29) Fragment. Langmuir. 2025;41(48):32495-32511. PMID 41263761.
3. Aidoukovitch A, Bankell E, Svensson D, Nilsson BO. Vitamin D triggers hCAP18/LL-37 production: Implications for LL-37-induced human osteoblast cytotoxicity. Biochem Biophys Res Commun. 2024;712-713:149962. PMID 38642493.
4. Memariani H, Memariani M. Antibiofilm properties of cathelicidin LL-37: an in-depth review. World J Microbiol Biotechnol. 2023;39(4):99. PMID 36781570.
5. Memariani M, Memariani H. Antifungal properties of cathelicidin LL-37: current knowledge and future research directions. World J Microbiol Biotechnol. 2023;40(1):34. PMID 38057654.
6. Suzuki K, Murakami T, Hu Z, Tamura H, Kuwahara-Arai K, Iba T, et al. Human Host Defense Cathelicidin Peptide LL-37 Enhances the Lipopolysaccharide Uptake by Liver Sinusoidal Endothelial Cells without Cell Activation. J Immunol. 2016;196(3):1338-47. PMID 26729811.
7. Koro C, Hellvard A, Delaleu N, Binder V, Scavenius C, Bergum B, et al. Carbamylated LL-37 as a modulator of the immune response. Innate Immun. 2016;22(3):218-29. PMID 26878866.
8. Wang G. Human antimicrobial peptides and proteins. Pharmaceuticals (Basel). 2014;7(5):545-94. PMID 24828484.
9. Suphasiriroj W, Mikami M, Shimomura H, Sato S. Specificity of antimicrobial peptide LL-37 to neutralize periodontopathogenic lipopolysaccharide activity in human oral fibroblasts. J Periodontol. 2013;84(2):256-64. PMID 22443521.
10. Zhang X, Oglęcka K, Sandgren S, Belting M, Esbjörner EK, Nordén B, et al. Dual functions of the human antimicrobial peptide LL-37-target membrane perturbation and host cell cargo delivery. Biochim Biophys Acta. 2010;1798(12):2201-8. PMID 20036634.
11. Golec M. Cathelicidin LL-37: LPS-neutralizing, pleiotropic peptide. Ann Agric Environ Med. 2007;14(1):1-4. PMID 17655171.
12. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, et al. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology. 2002;106(1):20-6. PMID 11972628.

Educational notice. This article is for educational and informational purposes only and is intended for licensed researchers and laboratory professionals. All scientific claims are referenced to primary peer-reviewed literature.

Research-only disclaimer. LL-37 is supplied as a research-grade reference compound for laboratory use only. It is not for human or veterinary use, and nothing on this page describes a route of administration or a quantity to use.