Introduction: The discovery of mutations in the copper-zinc superoxide dismutase (SOD1) gene on chromosome 21q21 marked a monumental breakthrough in neurogenetics
. Accounting for approximately 20% of familial ALS cases and 3% of sporadic cases, SOD1 encodes a vital homodimeric antioxidant metalloenzyme that catalyzes the conversion of superoxide radicals into molecular oxygen and hydrogen peroxide . Structural and Molecular Alterations:
Over 110 distinct mutations identified along the 12 kb gene containing five exons and four introns
. The most frequent mutation, A4V (Alanine-to-Valine substitution), induces rapid disease progression, short survival (~1 year), and prominent lower motor neuron findings with minimal upper motor neuron signs
. Mutations destabilize the native homodimeric state, impair copper and zinc binding, and reduce the net negative charge
.