ELANE (neutrophil elastase) is a serine protease with pleiotropic functions in innate immunity and tissue homeostasis. Primarily, ELANE kills gram-negative bacteria by digesting outer membrane proteins, particularly in E. coli and K. pneumoniae 1. ELANE also selectively kills cancer cells by proteolytically liberating the CD95 death domain, which interacts with histone H1 to induce cancer cell death while sparing non-cancer cells 2. Mechanistically, ELANE promotes cleavage of GSDMB to inhibit pyroptosis 3, enhances blood coagulation by inactivating tissue factor pathway inhibitor (TFPI) 4, and promotes platelet aggregation through integrin alpha-IIb/beta-3 activation 5. In metabolic dysfunction-associated fatty liver disease, ELANE enhances KEAP1 protein stability, reducing NRF2-mediated ferroptosis inhibition and promoting hepatocyte death 6. Disease relevance is significant: autosomal dominant ELANE mutations cause severe congenital neutropenia, characterized by impaired neutrophil maturation and life-threatening infections 7. Clinically, ELANE inhibition via brensocatib (a DPP-1 inhibitor) reduces sputum neutrophil elastase activity and decreases exacerbations in bronchiectasis patients 8, demonstrating therapeutic potential for chr19 inflammatory airway diseases 9.