TAR DNA-Binding Protein-43 (TDP-43) was first identified in 2001 as a protein able to bind the HIV-1 TAR binding sequence [61], and in 2006, as the main component of aggregates found in the brains of patients with ALS and FTLD [11,19] (Figure 1). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.