In animal models, Sig-1R KO mice exhibit the phenotypes of motor neuron degeneration, reduced ER-mitochondrial contacts, and perturbation of mitochondrial and calcium homeostasis [27]; depletion of Sig-1R in the SOD1∗G93A or SOD1∗G85R mouse also accelerates ALS progression and is accompanied by MAM disruption [25, 28]. Here, SIGMAR1 is linked to Motor neuron atrophy.