The recent discovery of several new calpain species other than the two species thus far studied reveals that calpain, especially the calpain large subunit, constitutes a family comprising at least six members that can be classified into ubiquitous (mu, m- and mu/m-types) and tissue-specific (p94 or nCL-1 specific for skeletal muscle, and nCL-2 and -2' specific for stomach) calpains. The newly identified tissue-specific calpains have various characteristics distinct from conventional calpains in structure, manner of expression, and enzyme activity. Unique features of tissue specific calpains are discussed together with the evolutionary view of the calpain large subunit.