The phenomenon of SOD1 misfolding is puzzling due to the protein’s remarkable stability (ΔΔG >20 kcal/mol) [4]; the mild destabilization (<5 kcal/mol) caused by ALS-linked mutations [5] does not significantly reduce the stability of SOD1 from that of the average human protein (~5–15 kcal/mol [6,7]), and so does not explain SOD1 misfolding [8,9]. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.