Who Is This Calpain Dude?

The calpains are a a family of neutral cysteine proteases that come in two flavors: calpain I (mu calpain) and calpain II (m-calpain). Calpain I lives in neurons, while calpain II seems to prefer hanging out in glia. Calpains need calcium to be proteolytically active, and are also regulated by calpastatin and activator proteins.

Figure. Ribbon diagram of calpain.

The physiologic role of calpain seems to be in modulating neurite outgrowth and remodeling of synapses. Synaptic activity, of course, is coupled to calcium flux across the membrane, and so it's easy to see how a protease linked to calcium flux could be useful in the controlled deconstruction of synaptic architecture. It's also easy to see how a huge flux of calcium--as occurs during brain ischemia--could cause calpain to just lose its frippin' mind and go over to the Dark Side.