While it has been shown that the metal-loaded forms of most of the mutant SOD1's are stable and hardly lose the metal ions once metalated as also holds for WT SOD1 [24], several ALS mutations have instead the largest effect on the most immature forms of SOD1; some mutations destabilize the metal-free and disulfide-reduced polypeptide to the point that these forms are unfolded at physiological temperatures [7], [25]. This evidence concerns the gene SOD1 and amyotrophic lateral sclerosis.