TARDBP and proteostasis deficiencies: However, in TDP-43 pathology, TDP-43 exits the nucleus, leading to the loss of nuclear function including in splicing regulation and the appearance of pathological events such as cryptic exons that seem to define at least the end-stage of TDP-43 proteinopathies (Cao et al., 2023; Ling et al., 2015; Ma et al., 2022).