Many ALS-variant SOD1 proteins exhibit mild-to-severely compromised affinity for both Cu2+ and Zn2+ (i.e., the binding affinity for mature A4V and G93A are Kd = 1.68 × 10−15 M and Kd = 6.09 × 10−17 M respectively for Zn2+) (20, 22). This evidence concerns the gene SOD1 and amyotrophic lateral sclerosis.