The detailed mechanism of how C9-HRE causes C9ALS/FTD is still unresolved, but previous studies have proposed that C9-HRE could form polymorphic secondary structures, including GQs in DNA and RNA levels which disturb the transcription and translation processes, leading to the loss of C9orf72 protein, the accumulation of RNA foci and the expression of neurotoxic dipeptide-repeat proteins (DPRs) [26,27]. The gene discussed is C9; the disease is frontotemporal dementia.