LL-37 is a natural peptide that can kill bacteria, attract immune cells, and cause neutrophils to throw out web‑like traps (NETs). These traps help fight infections but can also fuel chronic inflammation and tissue damage. The peptide’s shape changes to fit different environments, which may explain its varied effects.

Innate immunity responds to infections and inflammatory stimuli through a carefully choreographed set of interactions between cells, stimuli and their specific receptors. Of particular importance are endogenous peptides, which assume roles as defensins or alarmins, growth factors or wound repair inducers. LL-37, a proteolytic fragment of cathelicidin, fulfills the roles of a defensin by inserting into the membranes of bacterial pathogens, functions as alarmin in stimulating chemotaxis of innate immune cells, and alters the structure and efficacy of various cytokines. Here, we draw attention to the direct effect of LL-37 on neutrophils and the release of extracellular traps (NETs), as NETs have been established as mediators of immune defense against pathogens but also as important contributors to chronic disease and tissue pathogenesis. We propose a specific structural basis for LL-37 function, in part by highlighting the structural flexibility of LL-37 and its ability to adapt to distinct microenvironments and interacting counterparts.