In material from ALS and FTD patients with TDP-43 pathology, and in numerous TDP-43 disease models (yeast, cell culture, mouse, flies), either expressing wild-type TDP-43, disease-associated TDP-43 variants, TDP-43 fragments, or with TDP-43 knock-down, hallmarks of mitochondrial damage and dysfunction were observed. Here, TARDBP is linked to frontotemporal dementia.