The recent identification of an expanded hexanucleotide repeat in C9ORF72 as a frequent cause of the ALS/FTD clinical spectrum in addition to causative mutations in RNA-binding proteins, including TDP-43, FUS, sentaxin, and angiogenin, strongly implicates defects in RNA metabolism as a critical pathogenic pathway in both ALS and FTD[29,56-59]. This evidence concerns the gene TARDBP and frontotemporal dementia.