As with other genetically complex diseases, traditional linkage or candidate gene approaches were responsible for the discovery of the most highly penetrant ALS genes, including C9orf72 (DeJesus-Hernandez et al., 2011; Renton et al., 2011), SOD1 (Rosen, 1993), and FUS (Kwiatkowski et al., 2009). The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.