VCP and amyotrophic lateral sclerosis: Autosomal dominant mutations in VCP account for up to 1% of all ALS cases and, while the exact cause of MN dysfunction in these patients is unknown, mutations have been associated with both loss-of-function and gain-of-function effects.37,59–63 Our findings suggest that alterations in VCP function play a role in mutSOD1 toxicity, while VCP can modulate the degradation of insoluble mutSOD1 protein, linking two distinct genetic causes of ALS.