Cathepsin B (CTSB) is a lysosomal cysteine protease. While most cathepsins are exclusively endopeptidases, CTSB exhibits both carboxypeptidase and endopeptidase activities. The optimal pH for CTSB activity is between four and six. Cystatin C has been identified as an endogenous CTSB inhibitor. High CTSB protein levels and activities have been found in many tumors including breast, cervix, colon, stomach, glioma, lung, and thyroid tumors. CTSB can be secreted by tumor cells and is associated with the cell membrane of these cells. Membrane associated CTSB promotes extracellular matrix (ECM) degradation contributing to cancer motility and invasion. Many ECM proteins, including laminin, fibronectin, and collagen IV, are substrates of CTSB. CTSB can also activate pro-uPA/PLAU. Activated uPA promotes ECM digestion through serine protease plasminogen. It has been shown that the inhibition of CTSB can limit bone metastasis in breast cancer, making it an important anti-cancer drug target. CTSB has been proposed as a new drug target for Alzheimer's disease because of its involvement in the production of neurotoxic β-amyloid (Aβ) peptides. The inhibition of CTSB can reduce the brain Aβ peptides and improve memory determined from a mouse model with Alzheimer's disease. CTSB also plays significant roles in immune responses including both T and B cell apoptosis and Th1/Th2 polarization. CTSB is implicated in other pathological conditions including cardiovascular disease, multiple sclerosis, and arthritis. Roles of CTSB in autophagy, adipogenesis, and cholesterol absorption in the intestine have also been studied.