SOD1 and TDP-43 are the most widely studied animal models of ALS/FTLD, and there are several important recent studies manipulating SOD1 and TDP-43 genes (knock-out, conditional knock-out, knock-in, over-expression of the endogenous or human protein, mutations) to decipher metabolic changes in these animals and utilizing these findings for pre-clinical trials of metabolism-based therapeutic strategies. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.