Thus, our finding suggests that the ALS-associated Tdp-43 M337V mutation affects Tdp-43 function as splicing regulator of Mtfr1 under oxidative stress, and that over-expression of Oxr1-C rescues abnormal splicing dysregulation associated with Tdp-43 M337V. Here, MTFR1 is linked to amyotrophic lateral sclerosis.