Calpains activate during ischemia and contribute to the death of neurons.32 We have previously reported that calpain activation mediates GD-induced neuronal damage in hippocampal cultures.5 Calpain activity can lead to the cleavage of certain proteins at the lysosome membrane, such as Hsp70.1 (ref. 33), LAMP2 (ref. 34) and subunit b2 of v-ATPase,35 leading to LMP. The gene discussed is LAMP2; the disease is ischemia.