An expanded GGGGCC intronic repeat mutation in the gene C9ORF72 is the most common familial cause of both FTD and ALS.12,13 It has been proposed to mediate toxicity via three potential mechanisms: haploinsufficiency of C9ORF72, toxicity mediated via the production of repeat RNA, or production of toxic dipeptide repeat proteins (DPRs) via translation of repeat RNA.137 Despite intense scrutiny since the 2011 discovery of this mutation, no single mechanism has emerged as the clear driver of pathology. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.