Cathepsin C role in inflammatory gastroenterological, renal, rheumatic, and pulmonary disorders

Cathepsin C (CatC, syn. Dipeptidyl peptidase I) is a lysosomal cysteine proteinase expressed in several tissues including inflammatory cells. This enzyme is important for maintaining multiple cellular functions and for processing immune cell-derived proteases. While mutations in the CatC gene were reported in Papillon-Lefèvre syndrome, a rare autosomal recessive disorder featuring hyperkeratosis and periodontitis, evidence from clinical and preclinical studies points toward pro-inflammatory effects of CatC in various disease processes that are mainly mediated by the activation of neutrophil serine proteinases. Moreover, tumor-promoting effects were ascribed to CatC. The aim of this review is to highlight current knowledge of the CatC as a potential therapeutic target in inflammatory disorders. [Display omitted] •Cathepsin C activates granule serine proteinases involved in inflammation.•Cathepsin C contributes to the pathogenesis of different acute and chronic diseases.•Potential of cathepsin C inhibition to ameliorate inflammation in preclinical models.•Need for studies evaluating CatC inhibitors repurposing in chronic inflammatory diseases.