Importantly, there is a growing need to appreciate the extent of TDP-43 pathology beyond the context of traditional neurodegenerative disease silos to determine if moving from clinical syndromes to biological definitions of disease (as with Alzheimer’s disease5, Huntington’s disease6, and neuronal α-synuclein disease7) could be appropriate for TDP-43 proteinopathies8. Here, TARDBP is linked to neurodegenerative disease.