We previously described abnormal modification as well as altered localization of SigR1 protein in sALS patient spinal cord.11 Mavlyutov et al. demonstrated that lack of SigR1 exacerbates ALS progression in G93A-SOD1 mice.12 SigR1−/− mice showed MND pathology and symptoms.13In vitro, SigR1 depletion causes Ca2+ dysregulation, autophagy defects and ER stress-mediated neuronal death.11, 14 Furthermore, a SigR1 agonist improved motor function and MN survival in SOD1 mice.15 These studies suggest a crucial role of SigR1 for neuronal survival. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.