There are two kinds of ubiquitous calpains, calpain Ⅰ and calpain Ⅱ, differing in their Ca²⁺ requirements for half maximum activities. Both calpains have a large subunit and a small subunit, with molecular weights of 80 and 30 ku respectively. Large subunit is composed of 4 domains. Small subunit is composed of 2 domains. Recently, several tissue specific calpains were discovered, adding to the complexity of calpain system. Calpastatin is an endogenous suppressor of calpain, which can bind to activated calpain specifically and made them inactive. There are 5 domains in calpastatin, domain L and 4 repeated domains numbered 1 to 4 which are responsible for their inhibity effects. Calpain activity is restrictively regulated in living cells. Membrane attachment reaction can low the Ca²⁺ requirement of calpain to be activated. The negatively charged phosphate groups on the polar head of membrane phospholipids are inportment for that activation. Autolysis also can low the Ca²⁺ requirement of calpain.