TARDBP and amyotrophic lateral sclerosis: Indeed, depletion of TDP-43 results in early embryonic lethality in mice [40, 76], promotes cellular deficits such as the impairment of autophagy through down-regulation of Atg7 [8] and alteration of fat metabolism via suppression of Tbc1d1 [14], and causes ALS-like phenotypes in mice [74].