The role of the C9-HRE in ALS and FTD pathogenesis has been explored in the context of three possible disease mechanisms: loss-of-function, or decreased expression of endogenous C9orf72 protein, toxic gain-of-function of mutant sense and antisense repeat RNA, and toxic gain-of-function of RAN-translated dipeptide repeat proteins (DPRs): poly-Glycine-Arginine (polyGR), poly-Proline-Arginine (polyPR), poly-Glycine-Alanine (polyGA), poly-Glycine-Proline (polyGP), and poly-Proline-Alanine (polyPA) (Yang et al., 2020). This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.