Intriguingly, a SOD1 Leu117Val missense mutation which yields a mutant protein indistinguishable from wild-type SOD1 (in terms of its activity, stability and folding) causes amyotrophic lateral sclerosis, but with unusually low penetrance and slow progression (Synofzik et al. 2012). Here, SOD1 is linked to amyotrophic lateral sclerosis.