Similar to the TDP43 model, combining LDHB MNKO with Sod1D83G/D83G also led to significantly earlier and more severe motor deficits (Fig. 5), demonstrating that dysregulated lactate metabolism is a significant motor neurodegeneration risk synergizing with ALS risk factors acting via disparate mechanisms. The gene discussed is LDHB; the disease is amyotrophic lateral sclerosis.