Cathepsin C (CTSC) is a cysteine-type thiol protease with dipeptidylpeptidase activity that functions as both an exopeptidase and endopeptidase 1. Its primary physiological role involves activating serine proteases, particularly neutrophil serine proteases (NSPs) such as elastase, cathepsin G, and granzymes during neutrophil maturation 12. CTSC's disease relevance spans multiple pathologies centered on neutrophil-mediated inflammation. In breast cancer, tumor-secreted CTSC promotes lung metastasis by activating proteinase 3 to trigger IL-1β processing and neutrophil extracellular trap (NET) formation 3. During lung ischemia-reperfusion injury and pulmonary fibrosis, macrophage-derived CTSC similarly drives NETosis via NADPH oxidase activation and cleaves ICAM1 to promote fibroblast activation 45. CTSC expression also increases in myeloid cells during pancreatic cancer progression 6. Clinically, CTSC inhibition shows therapeutic promise. The reversible CTSC inhibitor BI 1291583 demonstrated dose-dependent efficacy in reducing pulmonary exacerbations in bronchiectasis patients 7, while AZD7986 sustained neutrophil elastase inhibition in healthy subjects 2. CTSC also represents a putative protective target in diabetic nephropathy treatment 8. These findings establish CTSC as a critical regulator of neutrophil-driven inflammation across diverse pathological contexts.