Mutations in FUS/TLS, as well as in the RBP TAR DNA-binding protein 43 (TDP-43), were found to be causative of familial cases of amyotrophic lateral sclerosis (ALS) [15, 16, 86], further implicating altered RNA metabolism as a central feature of these diseases. Here, TARDBP is linked to amyotrophic lateral sclerosis.