Indeed, rare disease-causing mutations in TARDBP, the gene encoding TDP-43, suggest that TDP-43 dysfunction is sufficient to cause ALS (Van Deerlin et al., 2008; Gitcho et al., 2008; Kabashi et al., 2008; Sreedharan et al., 2008), although the mechanism by which these mutations cause disease is unclear. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.