The mechanism(s) by which the repeat causes neuronal death in the motor cortex, brainstem and spinal cord in ALS and/or neuronal death in the frontal and temporal lobes of the brain in FTD are currently being elucidated, with three hypotheses proposed which are not mutually exclusive: (1) Haploinsufficiency of C9ORF72; (2) RNA toxicity; and (3) Dipeptide repeat protein (DPR) toxicity. Here, C9orf72 is linked to amyotrophic lateral sclerosis.