Kathepsiin

Kathepsiin is a lysosomal cysteine protease belonging to the papain-like cathepsin family. It is typically produced as an inactive zymogen containing a propeptide that blocks the active site; activation occurs in acidic compartments by proteolytic removal of the propeptide. The mature enzyme employs a catalytic cysteine-histidine dyad to hydrolyze peptide bonds and adopts the well-characterized papain-like fold.

Substrate preference is broad and context-dependent, enabling cleavage of extracellular matrix proteins, cytosolic and lysosomal substrates, and peptide antigens; some isoforms exhibit endopeptidase activity with selectivity for hydrophobic residues at the scissile bond.

Localization: predominantly in lysosomes across many animal cells; can also be secreted by certain cell types under physiological or pathological conditions, contributing to extracellular proteolysis.

Regulation and inhibitors: activity is controlled by lysosomal pH, redox state, and glycosylation; endogenous inhibitors such as cystatins and other protease inhibitors modulate kathepsiin activity to prevent excessive proteolysis.

Physiological roles and clinical relevance: kathepsiin participates in intracellular protein turnover, antigen processing for MHC class II presentation, and tissue remodeling. Dysregulation is associated in theory with inflammatory diseases, osteoporosis, and tumor invasion, motivating the development of selective inhibitors. However, as a hypothetical or less-well-characterized enzyme, specific therapeutic data remain limited.