Although the ALS-linked VAPB gene is rare and one of the least understood, the observation that VAP levels are decreased in sporadic ALS patients and animal models in which the VAPB gene is not mutated (such as mutant SOD1 mice) [147,149] is consistent with a general role of the VAPs in the pathogenesis of both SALS and FALS and suggests that elucidation of the cellular effects of the mutant gene will bring important insights into the molecular pathogenesis of ALS. This evidence concerns the gene VAPB and amyotrophic lateral sclerosis.