TARDBP and proteostasis deficiencies: Importantly, various hnRNPA1-targeting compounds have been developed and are currently being trialled in cancers.7 However, in contrast to the increased nuclear hnRNPA1 identified in most cancers32,33 the present findings of reduced nuclear hnRNPA1 in FTLD suggest the need for further studies to determine whether these compounds seeking to mediate nuclear loss or retain cytoplasmic hnRNPA17,34 will be appropriate for TDP-43 proteinopathies.