TARDBP and proteostasis deficiencies: TDP-43 levels increase with the normal ageing process in humans (Koike et al., 2021), and although TDP-43 pathology has also been reported in many healthy aged individuals (Uchino et al., 2015), the proportion of people with TDP-43 proteinopathy has been reported to be higher in patients with a neurodegenerative condition.