A2AR are particularly abundant in striatal medium spiny neurons of the indirect pathway, where they antagonize DA D2 receptor signaling and bolster the activity of this inhibitory pathway over-functioning in PD; this mechanism provides the rationale to understand the amelioration of motor function by the pharmacological or genetic blockade of A2AR in animal models of PD and PD patients (reviewed in [21,22]). Here, ADORA2A is linked to Parkinson disease.