DPP-1

Dipeptidyl peptidase 1 (DPP-1), also known as cathepsin C, is a lysosomal cysteine protease that activates granule-associated serine proteases by removing inhibitory N-terminal dipeptides^[1]. Mechanistically, DPP-1 supports neutrophil elastase, cathepsin G, and proteinase 3 activation, linking the target to neutrophil inflammatory pathways and tissue injury models^[2]. In DPPI-deficient mice, reduced neutrophil serine protease activation protected animals from acute experimental arthritis, supporting DPP-1 as a functional inflammation target^[2]. Compared with DPP-4, a serine exopeptidase that regulates incretin peptides, DPP-1 functions primarily as cathepsin C in lysosomal immune-protease maturation^[3][4]. For experimental applications, prolonged cathepsin C inhibition eliminated neutrophil serine protease activity, and brensocatib reduced bronchiectasis exacerbation risk in phase 2 and phase 3 trials^[5][6][7]. - DPP-1 assays can quantify downstream neutrophil elastase, cathepsin G, and proteinase 3 activity^[2]. - Cathepsin C inhibitors support bronchiectasis research focused on neutrophil-driven airway inflammation^[6][7]. - DPP-1 differs from DPP-4 by targeting immune serine-protease maturation rather than incretin degradation^[3][4].