Familial cases (fALS) account for 10–20% of all ALS, and up to 20% of fALS and ∼2% of sporadic ALS are caused by mutations in SOD1. However, although mutant SOD1 is now recognized to be the toxic moiety responsible for the selective death of motor neurons in SOD1-mediated ALS, the mechanism by which this protein exerts its toxicity is still not understood, and considerable effort is underway worldwide to analyse both the wildtype and mutant protein and to determine what causes death of motor neurons. Here, SOD1 is linked to amyotrophic lateral sclerosis.