Nuclear depletion and cytoplasmic aggregation of TAR DNA-binding protein-43 (TDP-43) is a key pathological feature in more than 97% of amyotrophic lateral sclerosis (ALS) cases and nearly 50% of frontotemporal dementia (FTD) cases (FTLD-TDP) [1–3]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.