The brain is a metabolically vulnerable and demanding organ that suffers acute degradation in performance when fuel is restricted. In recent years the Ryan lab has been dissecting the molecular basis of local ATP production in nerve terminals and discovered that many of the genetic drivers of Parkinsonism impact either the efficacy of ATP production or create undue metabolic burdens at synapses. We carried out a genetic suppressor screen for metabolically compromised synapse function and determined that PGK-1, the first ATP producing enzyme in glycolysis, is rate limiting and that modest changes in its activity confer strong protection against metabolic lesions, including those driven by certain PARK genes.