Cathepsin B (CTSB)

Cathepsin B (CTSB) is a lysosomal cysteine protease belonging to the papain superfamily of peptidases. Encoded by the CTSB gene, the protein is ubiquitously expressed across human tissues and is primarily localized within the endosomal–lysosomal compartment, where it participates in the degradation of intracellular proteins, extracellular matrix remodeling, and the processing of newly synthesized lysosomal enzymes. Like other cathepsins, CTSB undergoes proteolytic maturation after synthesis, transitioning from an inactive proform to a catalytically active enzyme in the acidic environment of the lysosome. It functions both as an endopeptidase and as a carboxydipeptidase, giving it a broad substrate range relative to related family members such as cathepsin D.

Beyond its homeostatic roles, CTSB has emerged as a clinically significant factor in oncology, neurodegeneration, and infectious disease. Elevated CTSB expression and secretion have been documented in multiple solid tumors—including pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer—where the enzyme contributes to tumor invasion, immune evasion, and therapy resistance. In the central nervous system, aberrant CTSB activity has been linked to lysosomal dysfunction in Parkinson's disease models, while in helminthic infection, parasite-derived cathepsin B homologs serve as immunodominant antigens. These diverse pathological associations have positioned CTSB as a tractable target for both small-molecule inhibition and enzyme-responsive drug delivery systems.