The pathogenesis of C9orf72-mediated ALS/FTD is associated with both a loss and gain of function, including the following: (1) loss-of-function mechanism: decreased transcription of the C9orf72 coding region that leads to reduced production of the C9ORF72 protein, also known as C9ORF72 haploinsufficiency; (2) gain-of-function mechanism: sense and antisense (GGGGCC)n RNA can sequester or alter the function of RNA-binding proteins and other proteins; (3) By non-AUG initiated translation: sense and antisense (GGGGCC)n RNA produce five toxic dipeptides repeat proteins (DPRs) (Figure 2). This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.