Familial ALS involving SOD1 is a case in point, wherein it has been shown that mutant SOD1 produces protein aggregation and that altered SOD1 enzymatic activity, low or high, is not responsible for pathogenesis (Bruijn et al., 1998), strongly suggesting it is aggregation of SOD1 itself (rather than SOD1 enzymatic activity) that produces/contributes to disease. Here, SOD1 is linked to amyotrophic lateral sclerosis.