Importantly, a single point-mutation that disrupts SARM1 catalytic activity is sufficient to negate the pro-degenerative effects of these ALS-associated variants, demonstrating the degenerative phenotype requires SARM1 NAD+ hydrolase activity and is not due to a non-specific mechanism such as the toxic aggregation of a misfolded protein. The gene discussed is SARM1; the disease is amyotrophic lateral sclerosis.