Dipeptidyl peptidase I (cathepsin C) (DPPI (also known as CatC or CTSC))

Dipeptidyl peptidase I (DPPI), also known as cathepsin C, is a lysosomal cysteine protease and the physiological activator of a wide range of serine proteases in immune and inflammatory cells, including neutrophil elastase, cathepsin G, proteinase 3, and the granzymes in cytotoxic lymphocytes[1][3][4][5]. It functions by removing dipeptides from the N-termini of protein and peptide substrates, a critical step for the activation of these proteases[3][5][6]. Structurally, DPPI is distinct among papain-like proteases by possessing a unique exclusion domain that restricts substrate access to the enzyme active site, conferring dipeptidyl peptidase specificity[1][4][6]. Mutations in the DPPI/CTSC gene cause inherited disorders such as Papillon-Lefèvre and Haim-Munk syndromes, characterized by defects in immune cell function and severe periodontitis[2][3]. DPPI is considered a validated therapeutic target for inflammatory diseases, and small-molecule inhibitors such as brensocatib are in development or clinical use to modulate excessive immune protease activation, notably in conditions like bronchiectasis[5]. However, safety concerns include the risk of compromising host defense and immune-mediated cancer surveillance when DPPI function is inhibited chronically[5].

Other names

Cathepsin CDPPIDPP-ICTSCdipeptidyl peptidase 1

Inhibition of activation of pro-serine proteases (e.g., neutrophil elastase, proteinase 3, cathepsin G, granzymes) Blockade of enzyme active site, preventing dipeptide removal and downstream protease activity