Cytoplasmic accumulation of TDP-43 has been regarded as a primary driver of neuronal toxicity and dysfunction [8, 9], however, loss of normal nuclear TDP-43 has also been reported even in the absence of cytoplasmic TDP-43 inclusions in post-mortem FTD [10, 11] and ALS brains [12]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.