LL-37

LL-37 is the 37-amino-acid antimicrobial peptide released from human cathelicidin hCAP18. It is studied for direct antimicrobial activity and immune-modulating effects in cell, animal and early human studies, and is not approved for any use.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

LL-37 is the only cathelicidin antimicrobial peptide found in humans. It is produced as part of a larger precursor protein, hCAP18, encoded by the CAMP gene, and is cleaved to its active form in neutrophils and other cells. Its name refers to its length of 37 residues and its two N-terminal leucines. It is expressed by neutrophils and by epithelial cells of the skin, airway and gut, where it forms part of innate immune defense.

Research on LL-37 spans microbiology, immunology and dermatology. It kills a range of bacteria, fungi and some viruses in vitro, binds bacterial lipopolysaccharide, and affects immune cell recruitment and activation. It is also implicated in inflammatory skin disease, notably psoriasis and rosacea. Expression of the CAMP gene is induced by vitamin D signaling, linking LL-37 to research on vitamin D and immunity.

Structure

LL-37 is a linear 37-residue peptide beginning with Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys and ending with Pro-Arg-Thr-Glu-Ser. It is strongly cationic, rich in lysine and arginine, and adopts an amphipathic alpha-helix in membrane-like environments, with a disordered structure in plain aqueous solution at low concentration. It tends to self-associate and form oligomers. It contains no cysteine, methionine or tryptophan. Its precursor, hCAP18, consists of an N-terminal cathelin-like domain and the C-terminal LL-37 domain, which is released by proteinase 3 in neutrophils; other proteases in skin generate shorter fragments.

Mechanism

Direct antimicrobial activity is attributed to interaction of the cationic, amphipathic helix with negatively charged microbial membranes, leading to membrane disruption. LL-37 also neutralizes lipopolysaccharide. Immune effects, described in cell and animal studies, include chemotaxis of immune cells through formyl peptide receptor 2, activation of the P2X7 receptor, transactivation of the epidermal growth factor receptor in epithelial cells, and modulation of Toll-like receptor signaling.

In psoriasis research, LL-37 has been shown to form complexes with self-DNA and self-RNA that activate plasmacytoid and myeloid dendritic cells through endosomal Toll-like receptors. These findings mean LL-37 can be pro-inflammatory as well as protective depending on context, which complicates its study as a therapeutic candidate.

Research

Antimicrobial studies

LL-37 has broad in-vitro activity against Gram-positive and Gram-negative bacteria, fungi and some enveloped viruses, and it can inhibit biofilm formation. Its activity is reduced by physiological salt concentrations, serum and some proteases, which limits direct extrapolation from simple assays. Many synthetic analogues and fragments have been designed to improve stability or selectivity, and these are a substantial research area in their own right.

Wound healing

Animal and cell studies have examined LL-37 in wound re-epithelialization and angiogenesis. A small early-phase human trial evaluated topically applied LL-37 in hard-to-heal venous leg ulcers and reported findings that its authors considered encouraging for further study. This evidence is limited in size, and LL-37 has not been approved for wound care. Larger controlled trials would be needed to establish any clinical effect.

Inflammatory skin disease

LL-37 is studied as a contributor to disease processes rather than a treatment. In psoriasis, LL-37-nucleic acid complexes are proposed to drive dendritic cell activation. In rosacea, elevated cathelicidin and abnormal processing into proinflammatory fragments have been described. This work is largely mechanistic, using human tissue samples, cell systems and mouse models. The findings have informed research on targeting LL-37 pathways in these conditions.

Vitamin D and immunity

The CAMP gene contains a vitamin D response element, and active vitamin D increases cathelicidin expression in several cell types. This has made LL-37 a focus of research on how vitamin D status relates to innate immunity and infection. Observational and mechanistic data are extensive, but they concern endogenous LL-37 regulation rather than administration of the peptide. Species differences matter here.

Regulatory status

LL-37 is not approved by the FDA for any use, and no LL-37 product is approved in the US. Its compounding status should be checked against current FDA lists. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A good certificate of analysis should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page, and report HPLC purity with the chromatogram. As a long synthetic peptide, LL-37 is prone to deletion and truncation impurities, which should appear as related-substance peaks. Its strong positive charge means it carries many counter-ions, so the salt form and net peptide content are important; residual TFA can itself affect cell-based assays. LL-37 aggregates and adsorbs to surfaces, so solubility behavior and the presence of oligomers may influence analytical and biological results. Endotoxin testing is relevant because LL-37 binds lipopolysaccharide, which can mask or confound endotoxin measurements.

Open LL-37 in the sequence analyzer to see the expected [M+H]⁺ and multiply charged ions for an MS identity check.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized LL-37 sealed at -20 °C or colder, protected from moisture and light, and equilibrate before opening. Although it lacks oxidation-prone residues, it is susceptible to aggregation and to adsorption onto glass and plastic, so low-binding tubes are advisable and concentrations should be verified after dissolution. Dissolve in water or dilute acid before adding to salt-containing buffers, which can promote aggregation. Aliquot solutions for frozen storage and avoid repeated freeze-thaw cycles.

Download the LL-37 data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• KPV

  KPV is the tripeptide lysine-proline-valine, the C-terminal sequence of alpha-melanocyte-stimulating hormone. It is studied for anti-inflammatory effects in cell and rodent models, particularly of intestinal inflammation, and is not approved for any use.

• Thymosin α1

  Thymosin α1 is a 28-amino-acid N-acetylated peptide derived from prothymosin α. Its synthetic form, thymalfasin (Zadaxin), is approved in several countries outside the US and has been studied as an immune modulator in clinical trials.

• VIP (vasoactive intestinal peptide)

  Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide of the secretin-glucagon family that acts on VPAC1 and VPAC2 receptors. It regulates smooth muscle, secretion and immune function, and synthetic VIP (aviptadil) has been studied clinically.

References

1. PubMed: all indexed literature on LL-37
2. ClinicalTrials.gov: registered studies mentioning LL-37