Cathepsin C: a critical mediator between immune response and cardiovascular disease–therapeutic implications of enzyme inhibition

Cathepsin C (CatC) is a lysosomal dipeptidyl peptidase that performs multiple physiological and pathological functions in the body. This review focuses on the complex biological roles of this enzyme in proteolytic networks, immune cell regulation, and cellular homeostasis. CatC is an enzymatic mediator that processes pro-inflammatory and cytotoxic precursors, such as neutrophil serine proteases, granzymes, and cathepsins. Recently, the role of CatC in inflammatory cascades, release, and immune modulation has extended far beyond its classical proteolytic function. Although CatC has been implicated in a wide range of pathologies, including autoimmune and neurodegenerative diseases, its therapeutic significance is unclear. The catalytic mechanism of sequential N-terminal dipeptide release offers the possibility of fine-tuning the proteolytic pathways. Genetic and biochemical evidence support its crucial role in cellular communication, inflammation, and immune regulation, making it an attractive candidate for therapeutic intervention. Emerging evidence suggests that CatC is a guardian molecule in pathogenesis and a novel therapeutic target. However, its multifunctionality necessitates specific interventions. This review synthesizes the findings, molecular mechanisms, and future perspectives, highlighting the potential of this enzyme to reshape therapeutic strategies for various diseases. For CatC inhibitors to reach their full therapeutic potential, barriers such as multifunctional regulation, systemic effects, and host-specific responses must be overcome in future studies. Omics technologies, biomarker discovery, combination treatments, and other novel approaches are expected to provide solutions for the management of inflammatory and immunological diseases, which would point toward addressing systemic diseases.