The interest in considering this synaptic A2AR-mediated control of excitotoxicity as a mechanism of PD evolution is bolstered by the recent claim that striatal DA deficits may not be sufficient to trigger the cascade of events leading to motor dysfunction [77], paving the way to incorporate the need for a simultaneous glutamatergic dysfunction, eventually resulting from the accumulation of α-synuclein [78,79], which is also controlled by A2AR [32,80]. The gene discussed is ADORA2A; the disease is Parkinson disease.