The majority of ALS cases are sporadic but a large group of dominantly inherited forms of the disease are caused by mutations in the gene encoding the abundantly expressed cytosolic superoxide dismutase-1 (SOD1).1,2 How SOD1 mutants provoke motor neuron degeneration remains to be elucidated, but it is now well established that SOD1 mutations cause familial ALS (fALS) by a gain of toxic properties and not by a loss of enzymatic activity. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.