Although the precise mechanism by which C9-HRE causes C9ALS/FTD is still unclear, the structure evaluation of long C9-HRE sequence and its conformation regulation in DNA as well as RNA level provides important potential for the C9-HRE related C9orf72 transcription and subsequential RNA foci and DPRs formation regulation. This evidence concerns the gene C9orf72 and frontotemporal dementia.