LL-37: Scientific Profile

Publicado el 12 de julio de 2026 · Actualizado el 28 de agosto de 2026

LL-37 (CAS 154947-66-7) is the only antimicrobial peptide of the cathelicidin family in humans, a cationic 37-residue fragment released from the precursor protein hCAP-18. Its dual mechanism combines disruption of microbial membranes with modulation of the innate immune response through receptors such as FPR2. Material intended exclusively for research use.

LL-37 is the mature, biologically active peptide fragment of human cathelicidin, the only protein of this family identified in humans. Its name derives from the two leucine residues (LL) that begin the sequence and from the 37 amino acids that compose it. LL-37 is generated by proteolytic cleavage of the C-terminal end of the precursor protein hCAP-18 (human cationic antimicrobial protein of 18 kDa), produced mainly by neutrophils, epithelial cells, keratinocytes, and monocytes. With molecular formula C205H340N60O53 and an approximate molecular weight of 4493.33 g/mol, it is classified among the cationic and amphipathic antimicrobial peptides, a group of central effectors of innate immunity that in research is studied for its role in the first line of defense against pathogens.

From a structural standpoint, LL-37 is a peptide with a strong net positive charge at physiological pH, attributable to its abundance of basic residues (lysine and arginine). In aqueous solution the peptide tends to remain relatively disordered, but upon contact with anionic membranes or environments with zwitterionic detergents it adopts an amphipathic alpha-helix conformation, in which the hydrophobic and hydrophilic faces are segregated along the helical axis. This amphipathicity is the feature that, in experimental models, is associated with its ability to interact selectively with lipid bilayers. LL-37 also shows a tendency to oligomerize, and its structural behavior depends on the ionic strength, the concentration, and the lipid composition of the system studied.

The mechanism of action of LL-37 documented in the preclinical literature is dual. On the one hand, it acts as a broad-spectrum antimicrobial agent: being cationic, it binds preferentially to the anionic components of microbial envelopes — lipopolysaccharide in Gram-negative bacteria, lipoteichoic acids in Gram-positive bacteria, and anionic phospholipids of the membranes — and, after reaching a critical density on the surface, it destabilizes membrane integrity. Several permeabilization models have been proposed ("carpet" type, toroidal pore formation) that explain the disruption of the electrochemical gradient and the cell lysis observed in vitro against bacteria, fungi, and some enveloped viruses. The relative selectivity toward microbial membranes over those of mammalian cells is attributed to differences in surface charge and cholesterol content.

The second axis of the mechanism, increasingly studied, is its immunomodulatory role. Beyond direct microbicidal activity, LL-37 functions as an innate immunity signaling molecule. In cell models it has been described that it binds and neutralizes lipopolysaccharide, modulating the inflammatory response; that it acts as a chemoattractant for neutrophils, monocytes, and T lymphocytes, in part through the formyl-peptide receptor FPR2 (also called FPRL1); and that it influences processes of angiogenesis, epithelial proliferation, wound healing, and the formation of complexes with self nucleic acids that can be recognized by innate immunity receptors. This latter property has made LL-37 an object of interest in research into the pathophysiology of inflammatory and autoimmune skin diseases, such as psoriasis and rosacea, as well as in studies on lupus, where complexes of LL-37 with DNA or RNA are being investigated as possible amplifiers of the immune response.

The documented research applications of LL-37 span several fields. In microbiology and in the preclinical development of antimicrobials, it is used as a reference molecule to study membrane permeabilization mechanisms and to explore strategies against bacterial resistance, given that peptides acting on membrane integrity represent a mode of action distinct from that of conventional antibiotics. In immunology, it is used as a tool to dissect the signaling pathways of innate immunity, chemotaxis and endotoxin neutralization. In experimental dermatology, LL-37 is a central model for investigating the skin barrier, wound healing and the pathogenesis of inflammatory dermatoses. It is also investigated in vascular biology models for its relationship with angiogenesis. It is important to note that much of this knowledge comes from in vitro systems and animal models, and that the role of LL-37 may be dual or even pro-inflammatory depending on the experimental context.

As for the level of evidence, LL-37 is one of the best-characterized human antimicrobial peptides: there is a broad and consistent body of preclinical literature — structural biochemistry, in vitro studies of antimicrobial and immunomodulatory activity, and animal models — that supports its dual mechanism. Nevertheless, it is not an approved drug, and the clinical translation of LL-37 and its analogs remains a matter of research; its context-dependent behavior, its sensitivity to ionic strength and to proteases, and its potential for pro-inflammatory effects are recognized limitations. For this reason, this material is offered strictly for laboratory research use, without any diagnostic indication or therapeutic application. Any work with LL-37 must be carried out in a controlled environment, with the appropriate experimental controls and with qualified personnel.