To these earlier efforts, our findings suggest that TDP-43 aggregation is not required to drive nuclear morphology aberrations as accumulation of mutant TDP-43 to only about the normal level of endogenously expressed TDP-43 in both neurons and glial cells drives progressive motor neuron disease with specific loss of a third of lower motor neurons, despite the absence of cytosolic accumulation of protein aggregates (nuclear or cytoplasmic) and loss of nuclear TDP-43 at any age [2]. This evidence concerns the gene TARDBP and motor neuron disorder.