-SOD1 (Superoxide Dismutase 1): Mutations in the SOD1 gene were the first identified genetic cause of ALS. SOD1 encodes an enzyme involved in antioxidant defense, and mutations in this gene can lead to protein misfolding and aggregation, mitochondrial dysfunction, and motor neuron degeneration. -C9orf72 (Chromosome 9 Open Reading Frame 72): Expansion of a hexanucleotide repeat sequence (GGGGCC) within the C9orf72 gene is the most common genetic cause of ALS and frontotemporal dementia (FTD). The exact mechanism by which the repeat expansion leads to neurodegeneration is not fully understood but likely involves RNA toxicity, protein aggregation, and impaired nucleocytoplasmic transport. -TARDBP (TAR DNA-Binding Protein): Mutations in the TARDBP gene, which encodes the TDP-43 protein involved in RNA processing and metabolism, have been identified in familial ALS cases. Abnormal accumulation of TDP-43 protein aggregates is a pathological hallmark of ALS. -FUS (Fused in Sarcoma): Mutations in the FUS gene, which encodes a DNA/RNAbinding protein involved in RNA processing and transport, have also been implicated in familial ALS. Like TDP-43, abnormal accumulation of FUS protein aggregates is observed in ALS. -Other Genes: Mutations in other genes, such as VCP (valosin-containing protein), OPTN (optineurin) and SQSTM1 (sequestosome 1) have been identified in rare familial ALS cases, although their contribution to disease pathogenesis is less well understood. Sporadic ALS (sALS) occurs in individuals with no family history of the disease and is thought to result from a combination of genetic susceptibility and environmental factors. While specific genetic mutations are less common in sALS compared to fALS cases, genome-wide association studies (GWAS) have identified common genetic variants associated with an increased risk of developing ALS. These variants are often found in genes involved in neuronal function, inflammation, and other biological pathways implicated in ALS pathogenesis. Genes associated with ALS based on data from the CAS Content Collection are explored in Figure to facilitate the identification of potential therapeutic targets and biological mechanisms underlying disease processes. A comprehensive table, including extensive details on genes, related proteins, expression profiles, function, and other related information, as well as multiple examples, is included in the Supporting Information, Table . ALS exhibits significant genetic heterogeneity, with different genetic mutations associated with distinct clinical phenotypes and disease progression. Additionally, genetic modifiers and environmental factors may influence the penetrance and expressivity of ALS-associated mutations, leading to variability in disease onset, severity, and progression among affected individuals. Understanding the genetic basis of ALS is critical for elucidating disease mechanisms, identifying potential therapeutic targets, and developing personalized treatment approaches for individuals with ALS. Ongoing research efforts continue to uncover novel genetic risk factors and pathways underlying ALS pathogenesis, with the ultimate goal of improving outcomes for patients with this devastating neurodegenerative disorder. The field of ALS research is experiencing a surge in novel developments Gene therapy targets specific genetic forms of ALS by introducing healthy copies of genes or using tools to silence mutated genes. Although gene therapy is still in early stages for ALS, it holds promise for personalized medicine in the future.