TARDBP and amyotrophic lateral sclerosis: Nucleocytoplasmic translocation of TDP-43 with formation of cytosolic pTDP-43 inclusions that might cause a nuclear LoF and cytoplasmic GoF toxicity is the prevailing neuropathology in sporadic ALS. The propagation of TDP-43 pathology in the CNS correlates with the spreading of the clinical symptoms [16].