SOD1 is a primary antioxidant enzyme that catalyzes the dismutation of superoxide radicals to prevent cellular damage 1. Beyond its canonical antioxidant role, SOD1 catalyzes oxidation of hydrogen sulfide to sulfate, detoxifying reactive sulfur species 2. SOD1 localizes to multiple cellular compartments including the cytosol, nucleus, and mitochondria, with nuclear presence particularly prominent in motor neurons 3. Mutations in SOD1 cause ~20% of familial ALS through a gain-of-toxic-function mechanism 45. Pathogenic SOD1 variants induce aberrant protein aggregation and oligomerization, with nucleation occurring through formation of inactive monomers, trimers, and hexamers with reduced disulfide bonds 6. Mutant SOD1 accumulates in nuclear compartments where it associates with NADPH oxidase activation, increased superoxide production, and progressive DNA damage 3. Additionally, oxidized SOD1 from ALS mutations impairs mitochondrial-derived vesicle formation and directly drives cellular senescence and premature aging 7. SOD1 aggregates appear in both familial SOD1-ALS and sporadic ALS cases, suggesting SOD1 seeding activity as a potential biomarker 8. Gene-silencing therapy with antisense oligonucleotides or tofersen targeting SOD1 mRNA extends survival in preclinical models and represents an emerging clinical treatment for SOD1-ALS patients 49.