Mutations in superoxide dismutase 1 (SOD1) account for up to 20% of genetic ALS cases, and to date ∼155 mutations have been identified.215 SOD1 is a metallo-enzyme that removes superoxide residues,216 and mutations lead to pathological aggregates of misfolded SOD1 in motor neurons and muscle217 Interestingly, SOD1 ALS does not present with TDP-43 pathology,218-220 suggesting an alternative pathogenesis in these cases. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.