We hypothesize that (1) the induction of metal cofactors for the stabilization of loop IV and VII, membrane interaction, and SOD1 aggregation would be some of the crucial elements in defining the overlapping folding-aggregation landscape of SOD1; (2) metal pocket perturbation by mutational stresses (as in disease variants) would modulate membrane association and facilitate aggregation, and (3) the difference in aggregate morphology as a result of differential membrane interaction may contribute to the variation in cellular toxicity observed in ALS. Here, SOD1 is linked to amyotrophic lateral sclerosis.