Recently, a mutation in Sig-1R was found in patients with a juvenile form of ALS,17 and PRE084 was shown to promote motoneuron survival in an animal model of ALS.23 We show here that the Sig-1R is decreased in neuronal PC6.3 after expression of mutant huntingtin proteins and can be restored by the agonist PRE084. The gene discussed is SIGMAR1; the disease is amyotrophic lateral sclerosis.