Since misfolded SOD1 is detectable in both sporadic and familial ALS, including in spinal cords of patients with the C9ORF72 expansion mutation19, we now propose that in all SALS, non-SOD1 and non-FUS FALS, pathological aggregation of wtTDP-43 triggers a prion-like cycle of propagated misfolding of HuWtSOD14. Here, SOD1 is linked to amyotrophic lateral sclerosis.