Cathepsin B (CTSB) is a lysosomal cysteine protease with diverse roles spanning protein degradation, tissue remodeling, and systemic signaling. Primarily, CTSB participates in intracellular protein turnover and cleaves extracellular matrix components including the phosphoglycoprotein MEPE 1. Beyond its classical proteolytic functions, CTSB operates as a myokine and intercellular signaling molecule with significant pathophysiological implications. In sepsis-induced acute kidney injury, elevated CTSB activity promotes lysosomal membrane permeabilization and activates mitochondrial apoptosis pathways in renal tubular cells; CTSB inhibition reverses this injury 2. During embryo implantation, blastocyst-derived CTSB induces pyroptosis in uterine epithelial cells, facilitating decidualization through IL-18-mediated signaling 3. Exercise-induced plasma CTSB correlates with enhanced hippocampal neurogenesis and spatial memory through BDNF-dependent mechanisms; CTSB knockout mice show impaired cognitive benefits from running 4. In cancer biology, glucose metabolism in tumor-associated macrophages drives CTSB O-GlcNAcylation and secretion, promoting metastasis and chemoresistance 5. Conversely, the endogenous CTSB inhibitor CST6 suppresses osteoclastogenesis and bone metastasis 6. During pancreatitis, macrophage-mediated CTSB-dependent trypsinogen activation amplifies inflammatory responses 7. These findings establish CTSB as a pleiotropic protease linking tissue homeostasis, metabolism, and systemic inflammation.