We have demonstrated that expression of hTDP-43 during early development yields a severe and complex phenotype (see Supplementary Table 2 for summary), including aggregation of phosphorylated TDP-43 and gliosis; however, these features are also accompanied by early lethality, extensive neuronal loss at an early age, TDP-43 inclusions that lack ubiquitin immunoreactivity and mitochondrial abnormalities that are not typical of human TDP-43 proteinopathies. Here, TARDBP is linked to proteostasis deficiencies.