Under physiological conditions, it is mainly a nuclear protein, while, in a pathological state, TDP43 shows nuclear depletion with concomitant cytosolic accumulation, protein truncation, and hyperphosphorylation with subsequent aggregation, so that both the loss of normal functions in the nucleus and the toxic gain of functions in the cytoplasm are considered to participate in TDP43 proteinopathy [1,12]. The gene discussed is TARDBP; the disease is proteostasis deficiencies.