Novel calpain-like protease polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length calpain-like protease proteins, the invention further provides isolated calpain-like protease fusion proteins, antigenic peptides, and anti-calpain-like protease antibodies. The invention also provides calpain-like protease nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a calpain-like protease gene has been introduced or disrupted. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.