Cathepsin C (CTSC) is a cysteine protease with dipeptidylpeptidase activity that activates serine proteases including neutrophil elastase, cathepsin G, and granzymes A and B. It functions as both an exopeptidase and endopeptidase, with substrate specificity excluding proline at the P1 position and arginine at the P2 position. CTSC operates in disease contexts through distinct mechanisms. In breast cancer, tumor-secreted CTSC activates neutrophil proteinase 3 to trigger interleukin-1β processing and nuclear factor κB activation, promoting neutrophil recruitment and formation of neutrophil extracellular traps that support lung metastasis 1. During lung ischemia-reperfusion injury, macrophage-derived CTSC similarly induces neutrophil NETosis via NADPH oxidase-mediated reactive oxygen species production and proteinase 3 activation 2. In pulmonary fibrosis, CTSC accumulates in the extracellular matrix where it cleaves ICAM1, promoting fibroblast activation 3. Clinically, CTSC inhibition represents a therapeutic opportunity in bronchiectasis, where uncontrolled neutrophil serine protease activity drives lung damage. The phase II AIRLEAF trial demonstrated that BI 1291583, a reversible CTSC inhibitor, produced dose-dependent reduction in exacerbation risk in adults with bronchiectasis 4. Additional CTSC inhibitors including AZD7986 have shown sustained neutrophil elastase inhibition in healthy subjects and preclinical efficacy in breast cancer metastasis models 5.