In this study, we demonstrate that this model effectively captures the key pathological hallmarks of ALS, including TDP-43 aggregation, genomic instability, neuroinflammation, senescence, and muscle wasting, while offering a promising approach for exploring the onset of DNA repair impairment and its associated pathology in ALS/FTD. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.