Calpain family (Calpain-1, Calpain-2, Calpain-9) (CAPN1/CAPN2/CAPN9)

Calpains are a family of calcium-dependent, intracellular, non-lysosomal cysteine proteases with important roles in controlling limited proteolysis of specific substrates, modulating diverse cellular processes including cell cycle, migration, apoptosis, and signal transduction. Calpain-1 and calpain-2 are classical isoforms ubiquitously expressed in mammals, differing primarily in their calcium requirements (with calpain-1 activated by micromolar and calpain-2 by millimolar calcium levels). Calpain-9 is more recently characterized and is spatially restricted, playing a key role in fibroblast activation and fibrotic disease. These proteases are implicated in neurodegeneration, cancer, fibrotic disorders, and muscle diseases, and are considered potential therapeutic targets, with several inhibitors under research or development.

Other names

μ-calpainmicro-calpainCANP Im-calpainmacro-calpainCANP IInCL-4 (novel calpain-like protease 4)

Inhibition of cysteine protease activity (blocking calcium-dependent substrate proteolysis) Reduction of pathological protein cleavage and downstream pathological signaling Anti-fibrotic effects (via inhibition of fibroblast differentiation, specific to calpain-9)