Calpain (family) (CAPN)

Calpains (CAPN family) are intracellular, calcium-dependent cysteine proteases ubiquitously expressed in mammalian tissues and many other organisms. They modulate a wide range of cellular processes through limited proteolysis of target proteins, affecting cellular architecture, signal transduction, cell motility, and apoptosis. There are at least 15 human CAPN genes, with individual family members having tissue- and context-specific roles. Deregulation of calpain activity has been implicated in a range of diseases, including cancer, neurodegeneration, and fibrosis, making specific family members attractive therapeutic targets. Research into calpain inhibitors continues, but clinical translation remains challenging due to the essential physiological functions of these enzymes in normal cell biology.

Other names

Calpain (generic family term)Calcium-activated neutral proteaseCalpain proteaseμ-calpain (CAPN1)m-calpain (CAPN2)calpain-6 (CAPN6)calpain-9 (CAPN9)

Inhibition of proteolytic activity by direct binding to calpain active site or allosteric sites (e.g., calpain inhibitors block substrate cleavage). They also modulate calcium-dependent activation, meaning inhibitors may disrupt Ca²⁺ requirement or conformational activation.