Several years after the appreciation of TDP-43 pathology in ALS, FTD, and IBM, the importance of this feature was underscored by the identification of ALS-causing mutations in the gene encoding this RBP (Gitcho et al., 2008; Kabashi et al., 2008; Kuhnlein et al., 2008; Rutherford et al., 2008; Sreedharan et al., 2008; Van Deerlin et al., 2008; Yokoseki et al., 2008; Pamphlett et al., 2009). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.