In this context, the nuclear clearance of TDP-43 and the accumulation of cytoplasmic TDP-43 aggregates represent the core pathobiology of TDP-43 proteinopathies, including almost all cases (97%) of amyotrophic lateral sclerosis (ALS) [19,20] and a considerable number of cases of frontotemporal lobar degeneration (FTLD) [21], comprising one of its clinical subgroups known as frontotemporal dementia (FTD) [22], and of Alzheimer’s disease [23]. The gene discussed is TARDBP; the disease is early-onset autosomal dominant Alzheimer disease.