Large hexanucleotide expansions in C9orf72 lead to neurodegeneration in ALS/FTD through the cooperation between loss and gain of functions, derived from C9orf72 haploinsufficiency and accumulation in patients’ brain and spinal cord of C9orf72 HRE bidirectional transcripts and cytoplasmic toxic aggregates of dipeptide repeat proteins (DPRs) [13]. Here, C9orf72 is linked to amyotrophic lateral sclerosis.