Calpain-1 or Calpain-2 (Calpain-1 (µ-calpain for Calpain I), Calpain-2 (m-calpain for Calpain II))

Calpain-1 and Calpain-2 are the two best-characterized members of the calpain family, a group of calcium-dependent, non-lysosomal cysteine proteases ubiquitously expressed in mammals[5][1]. Calpain-1 (also called µ-calpain) and Calpain-2 (also called m-calpain) are heterodimers, each consisting of a distinct large catalytic subunit (80 kDa) encoded by the CAPN1 (for Calpain-1) or CAPN2 (for Calpain-2) genes, and a common small regulatory subunit (28 kDa, CAPNS1)[1][5]. Activation requires calcium binding to multiple sites and induces conformational changes that align the catalytic triad for proteolytic activity[1][3][6]. Calpains do not function as degradative enzymes, but rather cleave specific peptide bonds in target proteins to modulate cell movement, signaling, and apoptosis in response to calcium influxes[1][5]. Dysregulation of calpain activity has been implicated in various pathologies, including neurodegenerative disorders (e.g., the activation of calpain-1 in Alzheimer’s disease), cancer, muscular dystrophy, and cardiovascular disease[4][5]. Calpain inhibitors are of pharmacological interest, but their clinical use is limited by concerns about selectivity and interference with normal physiological processes[1][5].

Other names

μ-calpain (mu-calpain)m-calpainCalcium-activated neutral protease ICalcium-activated neutral protease IICANP1 (for Calpain-1)CANP2 (for Calpain-2)CAPN1CAPN2

Inhibition of calcium-dependent cysteine protease activity Blockade of proteolytic cleavage of intracellular substrates