Synergistic effects with other ALS-related genes (1) Mutant TDP-43 A315T combined with the null mutation of alfa-1: • Alfa-1 expression decreases • Enhances the toxicity of mutant TDP-43 protein • Exacerbates the paralysis phenotype (2) Mutant FUS US5 combined with the null mutation of alfa-1: • Unenhanced the toxicity of mutant FUS proteins. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.