C9orf72 and amyotrophic lateral sclerosis: Since the identification of a GGGGCC (G4C2) repeat expansion within the first intron of C9orf72 as the major cause of both familial ALS and FTD1,2, a variety of mechanisms, including haploinsufficiency3, RNA toxicity4, and dipeptide repeat (DPR) toxicity5–7, have been proposed to explain the pathogenicity of this autosomal dominant mutation.