The observed death of motor neurons in SOD1-associated ALS (SOD1-fALS) may be caused by a gain of cytotoxic function resulting from mutant SOD1 aggregation-induced dysregulation of the ubiquitin-proteasome system, mitochondrial dysfunction, disruption of cytoskeletal elements, sequestration of essential proteins, and potential generation of reactive nitrogen or oxygen species2–4. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.