Although it remains to be elucidated whether RGC degeneration involves the mitochondrial μ-calpain and AIF-dependent pathway, the intracellular Ca2+ elevation in RGC [50] could trigger the activation of mitochondrial calpains as well as cytosolic calpains, and activated mitochondrial calpains would contribute to RGC death via AIF truncation/activation in glaucoma. The gene discussed is AIFM1; the disease is glaucoma.