SIGMAR1 and early-onset autosomal dominant Alzheimer disease: It is emerging as a unique pluripotent modulator of cell survival that interacts with many structurally diverse proteins.12, –14 Mutations of SIG1R are implicated in human neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease,15, , , , –20 whereas activating Sig1R has conferred neuroprotection in animal models of these diseases.21, –23