Despite strong evidence for the role of haploinsufficiency in C9ORF72 pathology, most published therapeutic approaches for C9-ALS/FTD, such as microRNA54,78 antisense oligonucleotide strategies12,79, and antibody therapies80 focus on reducing HRE gain-of-function but not rescue of haploinsufficiency. Here, C9 is linked to amyotrophic lateral sclerosis.