LL-37

LL-37 is the only human cathelicidin-derived antimicrobial peptide (AMP), consisting of 37 amino acids released by proteolytic cleavage of the human cationic antimicrobial protein (hCAP18) precursor. LL-37 is a key effector of the innate immune system, exhibiting dual functionality: direct antimicrobial activity and immunomodulatory signalling. As an antimicrobial peptide, LL-37's mechanism centres on its cationic (positively charged) amphipathic structure — the peptide has a net positive charge at physiological pH and a structure that segregates hydrophobic and hydrophilic residues. This allows LL-37 to bind to negatively charged bacterial cell membranes (which are enriched in lipopolysaccharide in Gram-negative bacteria and lipoteichoic acid in Gram-positive bacteria) and insert into the lipid bilayer, forming pores that disrupt membrane integrity and cause microbial cell death. Beyond direct antimicrobial activity, LL-37 functions as an immunomodulatory signalling molecule: it acts as a ligand for formyl peptide receptor 2 (FPR2), purinergic P2X7 receptor, and epidermal growth factor receptor (EGFR), modulating immune cell recruitment, cytokine production, and inflammation resolution. LL-37 also neutralises bacterial lipopolysaccharide (LPS) and lipoteichoic acid, preventing TLR4-mediated inflammatory cascade activation. In wound healing, LL-37 promotes re-epithelialisation and angiogenesis through EGFR transactivation.