SOD1 and amyotrophic lateral sclerosis: This argues one of two things: (1) that CuZnSOD mutations leading to ALS are not dependent upon SOD activity and based more on specific properties of the protein (i.e., ability to for inclusion bodies or protein aggregates [103,104,105]) or (2) the mutations cause differential localization of CuZnSOD leading to aberrant or deficient ROS signaling cascades.