From the identification of TDP-43 positive aggregates in the brains and spinal cords of ALS/FTD patients, to a genetic link between TARBDP mutations and the development of TDP-43 pathology in ALS, there is strong evidence indicating that TDP-43 plays a pivotal role in the process of neuronal degeneration. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.