The key breakthrough that led to this transformative understanding of ALS was the discovery that TDP-43 (TAR DNA binding protein, or transactive response DNA binding protein 43 kDa) accumulates in degenerating motor neurons and within degenerating cortical neurons in frontotemporal lobar degeneration (FTLD) (13, 14). Here, TARDBP is linked to amyotrophic lateral sclerosis.