Landmark discoveries showing the RNA-binding protein, transactive response DNA binding protein 43 (TDP-43 or TARDBP), as the main component of ubiquitinated inclusions in both familial and sporadic forms of ALS and FTD helped establish new models of protein-aggregate dependent neuronal dysfunction (Arai et al., 2006; Neumann et al., 2006). Here, TARDBP is linked to amyotrophic lateral sclerosis.