SERPINB1 (serpin family B member 1) is a neutrophil serine protease inhibitor that plays a critical role in regulating innate immunity and inflammation. Intracellularly, SERPINB1 protects cells from destructive proteases released during stress or infection by inhibiting elastase, cathepsin G, proteinase-3, and other serine proteases, as well as granzyme H and inflammatory caspases (CASP1, CASP4, CASP5) 1. This protective function is particularly important in neutrophils, where SERPINB1 prevents pathogenic activation of cell death pathways; downregulation of SERPINB1 following FcγR activation leads to caspase-1/11 activation and gasdermin D-mediated cell death in systemic lupus erythematosus 2. Beyond immunity, secreted SERPINB1 promotes pancreatic β-cell proliferation via its protease inhibitory function, suggesting therapeutic potential in diabetes 3. SERPINB1 also possesses dual enzymatic activities—antiprotease and endonuclease functions—with roles in cell migration and potentially wound healing 4. Disease relevance extends to acute lung injury, where SERPINB1 is rhythmically regulated by Rev-erbα and protects against lipopolysaccharide-induced neutrophil extracellular trap formation 5. Notably, Mendelian randomization studies identified SERPINB1 as a validated druggable target for Alzheimer's disease treatment with no apparent adverse effects 6, while loss of SERPINB1 expression contributes to hand-foot skin reactions caused by tyrosine kinase inhibitors 7.