C9orf72 and amyotrophic lateral sclerosis: In C9orf72-FTD/ALS, gain-of-function mechanisms emanating from the repeat are proposed to be the dominant cause of neurodegeneration (Mizielinska et al., 2014; Moens et al., 2019), and both repeat RNA and DPRs can affect the autophagy-RNA homeostasis interplay.