The Calpain Proteolytic System

The calpain proteolytic system is present in most living organisms and is a critical element of protein homeostasis. Its fifteen family members have different cellular distributions, with some members ubiquitously present, while others are restricted to certain tissues/organs. While much has been learned since its discovery in 1964, there remains significant gaps regarding the regulation and functions of many of the calpain isoforms. This article reviews what is known of the physiological functions and signaling pathways of calpains, and of the various disorders they are directly or indirectly involved in. Finally, recent clinical implications of the basic findings are discussed.