Therefore, future studies should aim to elucidate the potential synergistic roles of both gain-of-function mechanisms (i.e., DPR-mediated disruption of glycolysis) and loss-of-function mechanisms (i.e., de-stabilization of the ETC), as both would be expected to occur in human C9orf72-ALS/FTD carriers and contribute to energy imbalance. Here, C9orf72 is linked to amyotrophic lateral sclerosis.