These results together highlight the extreme criticality of the initial folding of nascent hSOD1 induced by Zn2+, implying that the failure to achieve the initial folding may render WT-hSOD1 to become as toxic as the ALS-causing mutants, thus representing a convergent mechanism for the mutant hSOD1 to cause FALS and WT-hSOD1 to trigger SALS. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.