Despite such a richness of experimental paradigms, however, it has still to be definitively clarified as to whether SOD1-related ALS forms were initiated by a detrimental loss of activity of the enzyme, or acquisition of novel neurotoxic properties of the protein—possibly caused by cell intoxication by misfolded and aggregated protein conformers—or both mechanisms. Here, SOD1 is linked to amyotrophic lateral sclerosis.