Mutations in superoxide dismutase 1 (SOD1) are a major cause of familial 
amyotrophic lateral sclerosis (ALS), whereby the mutant proteins misfold and 
aggregate to form intracellular inclusions. We report that both small 
ubiquitin-like modifier (SUMO) 1 and SUMO2/3 modify ALS-linked SOD1 mutant 
proteins at lysine 75 in a motoneuronal cell line, the cell type affected in 
ALS. In these cells, SUMO1 modification occurred on both lysine 75 and lysine 9 
of SOD1, and modification of ALS-linked SOD1 mutant proteins by SUMO3, rather 
than by SUMO1, significantly increased the stability of the proteins and 
accelerated intracellular aggregate formation. These findings suggest the 
contribution of sumoylation, particularly by SUMO3, to the protein aggregation 
process underlying the pathogenesis of ALS.