Mutations in superoxide dismutase 1 (SOD1) associated with familial amyotrophic lateral sclerosis(fALS) induce the protein to misfold and aggregate. To date, missense mutations at more than 80 different amino acid positions have been associated with disease. How these mutations perturb native structure to heighten the propensity to misfold and aggregate is unclear. One potential mechanism that has been suggested is that when mutations occur at positions occupied by charged amino acids, then repulsive forces that would inhibit aberrant protein:protein interactions would be reduced. Mutations at twenty-one charged residues in SOD1 have been associated with fALS.Here, we examined whether loss of positively charged surface Lys residues would induce the misfolding and aggregation of SOD1. We randomly mutated four different Lys residues (K30, K36, K75, K91) in SOD1 and expressed these variants as fusion proteins with yellow fluorescent protein (YFP). We also assessed whether these mutations induced binding to a conformation-restricted SOD1 antibody, designated C4F6, which recognizes non-natively folded protein. Our findings indicate that SOD1 generally tolerates mutations at surface exposed lysine residues, and that loss of positive charge is insufficient to induce aggregation. Our findings may explain why mutations at these Lys residues have not been identified in ALS patients.