Calpain 1, also designated micro-calpain, is an intracellular calcium-dependent protease that cleaves cyto-skeletal and submembranous proteins. Calpains are nonlysosomal, calcium-activated intracellular cysteine proteases. Calpains mediate specific Ca2+-dependent processes including cell fusion, mitosis and meiosis. Calpains are heterodimers of a small regulatory subunit and one of three large catalytic subunits, designated Calpain 1, Calpain 2 and Calpain p94. Calpain-1 co-localizes with human leukocyte antigen-DR (HLA-DR) on activated microglia in the aging brain. Calpain influences the process of spermatogenesis and the events preceding fertilization, such as the acrosome reaction.