TDP-43 proteinopathy is a key neuropathological feature in the CNS of ALS patients and frontotemporal lobar degeneration (FTLD) patients and appears in forms of cytoplasmic-mislocalization, hyperphosphorylation, intranuclear, and cytoplasmic aggregates; a loss of nuclear TDP-43 leads to altered transcriptomic profiles and chromatin decondensation [114,119]. Here, TARDBP is linked to amyotrophic lateral sclerosis.