The pathogenic role of C9ORF72 is still controversial, but increasing evidence indicates that the pathogenic mechanism of C9ORF72-ALS involves a cascade of reactions, including multiple cellular mechanisms: (1) G4C2 hexanucleotide repeat expansion causes RNA toxicity [40, 41]; (2) aggregation of toxic dipeptide repeat proteins (DPRs) translated from the hexanucleotide repeats through repeat-associated non-ATG translation [42, 43]; and (3) decreased levels of normally functioning C9ORF72 protein, leading to loss-of-function mechanisms [44]. Here, C9orf72 is linked to amyotrophic lateral sclerosis.