SIGMAR1 and amyotrophic lateral sclerosis: The key role of the SIGMAR1/Sigma-1 receptor in ALS is demonstrated in human genetic studies showing that an autosomal recessive juvenile form of ALS is with the loss-of-function E102Q mutation of SIGMAR1 [79], while patrial loss-of-function mutations in SIGMAR1 cause an adult-onset ALS, demonstrating a dose-relation between SIGMAR1 function and disease severity.