TARDBP and proteostasis deficiencies: Notwithstanding there are no clear data of age-related changes in TDP-43 in human82,83, altogether these observations suggest that a better understanding of the mechanisms and factors involved in controlling the activity of the TARDBP promoter and, consequently, TDP-43 expression will give clues to uncover novel processes implicated in the onset and progression of the TDP-43 proteinopathies.