SOD1 and amyotrophic lateral sclerosis: The aggregation of unstable Sod1 was originally thought to trigger fALS as a result of concurrent loss in Sod1 enzymatic activity (Deng et al., 2006); however, mice lacking the SOD1 gene do not develop ALS (Reaume et al., 1996) and therefore a toxic gain-of-function is thought to underlie ALS-associated pathology.