Molecular Classification
Enzyme, Cysteine protease
Other Names
Calcium-activated neutral protease, CANP, μ-Calpain, m-Calpain, Calpain I, Calpain II
Disease Roles
Neurodegenerative diseaseCardiovascular diseaseStroke

Calpain Overview

Calpains are a family of intracellular, calcium-dependent, non-lysosomal cysteine proteases. They are ubiquitously expressed in mammals and many other organisms, playing key roles in various cellular processes by mediating limited proteolysis of specific substrates. The calpain system includes the calpain proteases themselves, a small regulatory subunit (CAPNS1/CAPN4), and an endogenous inhibitor called calpastatin. Dysregulation or overactivation has been implicated as an aggravating factor in various diseases including neurodegeneration after trauma/stroke/myocardial infarction due to excessive substrate cleavage following abnormal increases in intracellular Ca²⁺ levels.

Mechanism of Action

Calpain inhibitors (being developed) aim to reduce excessive proteolysis following calcium dysregulation.

Biological Functions

Cytoskeleton remodeling
Signal transduction
Apoptosis
Cell cycle control

Disease Associations

Neurodegenerative disease
Cardiovascular disease
Stroke
Ischemia
Myocardial infarction

Safety Considerations

  • Potential for off-target effects due to broad substrate specificity.
  • Inhibition of calpain activity may have unintended consequences on normal cellular function.