The RNA-binding protein TDP-43 shuttles between the nucleus and the cytosol [73] and accumulation of cytoplasmic TDP-43 has been observed in the CNS of patients with FTLD and ALS, including C9-HRE carriers, indicating altered subcellular localization [18, 66–68], Examination of TDP-43 subcellular localization demonstrated that TDP-43 is strongly localized in the nucleus in all fibroblasts (Fig. 6a). Here, TARDBP is linked to amyotrophic lateral sclerosis.