Loss-of-function of C9ORF72 is insufficient to lead to ALS/FTD and no truncating mutations associated with ALS/FTD have been reported in this gene, but recent evidence suggests that C9ORF72 haploinsufficiency could contribute to disease pathogenesis by worsening the repeat-dependent gain-of-function mechanisms [79]. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.