Although still debated, mounting evidence suggests that C9ORF72-ALS pathogenesis is the result of a cascade of multiple cellular mechanisms that include: (i) RNA toxicity depending on G4C2 hexanucleotide repeat expansions (HRE) [57,58]; (ii) aggregation of toxic dipeptide repeat proteins (DPR) produced from the HRE region through Repeat-Associated Non-ATG (RAN) translation [59,60,61]; (iii) reduced levels of C9ORF72 protein causing disease by loss-of-function mechanisms [62]. The gene discussed is C9orf72; the disease is amyotrophic lateral sclerosis.