CTSB

Cathepsin B (CTSB), a lysosomal cysteine protease encoded by the CTSB gene, plays dual roles in intracellular protein degradation and extracellular matrix remodeling. Also known as APPS or CPSB, it functions as both an endopeptidase and exopeptidase, activated in acidic environments. CTSB regulates critical pathways including NF-κB signaling, TGF-β-mediated EMT, and PI3K/AKT/mTOR cascades, influencing tumor invasion, angiogenesis, and apoptosis. Its overexpression correlates with aggressive cancers (glioblastoma, pancreatic adenocarcinoma), neurodegenerative disorders (Alzheimer's disease via amyloid-β processing), and inflammatory conditions (rheumatoid arthritis). Pharmaceutical targeting focuses on selective inhibitors like CA-074 and its prodrugs, which have shown preclinical efficacy in reducing metastasis and chemotherapy resistance. Recent phase I trials explore CTSB inhibitors combined with immunotherapies, leveraging its role in modulating tumor microenvironment antigen presentation. Paradoxically, CTSB deficiency exacerbates atherosclerosis through impaired lipoprotein processing, highlighting context-dependent therapeutic implications.