CELA1 (chymotrypsin-like elastase 1) is a serine protease that functions as a stretch-dependent elastinolytic enzyme primarily in the lung. 1 CELA1 exhibits pancreatic elastase-like activity 2 and is activated by trypsin cleavage. 2 In normal physiology, CELA1 participates in postnatal lung remodeling and elastin homeostasis in response to mechanical strain. 1 Mechanistically, CELA1 binds and cleaves lung elastin in a stretch-dependent manner, and is the sole source of stretch-inducible lung elastase activity. 1 Alpha-1 antitrypsin (AAT) covalently neutralizes CELA1 in vivo, regulating its protease activity. 1 CELA1 is pathologically relevant to emphysema development across multiple contexts. In AAT-deficient emphysema, CELA1 expression is upregulated, and Cela1-knockout mice are completely protected against disease. 1 Similarly, CELA1 contributes to emphysema in non-AAT-deficient models including pancreatic elastase injury, cigarette smoke exposure, and aging. 3 Notably, CELA1 mutations have been identified as candidate susceptibility genes for Balkan endemic nephropathy, a progressive renal disease, suggesting roles in basement membrane/extracellular matrix biology beyond the lung. 4, 5 Clinically, anti-CELA1 antibody KF4 prevents emphysema progression in multiple models and represents a potential lung matrix-stabilizing therapeutic approach. 3