Haploinsufficiency was suggested as a potential disease mechanism in C9-FTD/ALS in the initial reports characterizing C9orf72 HRE (Dejesus-Hernandez et al., 2011; Renton et al., 2011; Gijselinck et al., 2012), and evidence in support of this idea soon emerged in model organisms (Ciura et al., 2013). This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.