Because C9orf72 ALS is remarkably common, great effort has been placed on defining its mechanistic basis, and three leading models for disease pathogenesis have emerged: (1) RNA gain-of-function, (2) loss of C9orf72 normal function, and (3) production of toxic dipeptide repeat (DPR) proteins via Repeat Associated Non-ATG (RAN) translation. Here, C9orf72 is linked to amyotrophic lateral sclerosis.