p94 belongs to the calcium-dependent cysteine protease (calpain) family which has been detected from human to mold. In contrast to the conventional m- and mu-calpains which are expressed ubiquitously, expression of p94 predominates in skeletal muscle, and the mRNA for p94 is at least 10-times more abundant than mRNAs encoding in the m- and mu-types. The unique feature of p94 is that it undergoes rapid and exhaustive autolysis with a half-life of less than half an hour. To elucidate the nature of specific and abundant expression in skeletal muscle, and to proceed toward gene targeting p94, we have cloned and characterized mouse and rat genes for p94, and compared them with that of the human sequence. The sequence comparison among three mammalian species revealed several conserved regions including possible transcription factor binding sites. Furthermore, mouse and rat upstream regions of p94 are conserved over 3 kb suggesting that expression of p94 in skeletal muscle of both rodents is similarly regulated.