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G protein-coupled receptor 37 (GPR37), also known as parkin associated endothelin-like (Pael) receptor, is an orphan G pro-tein-coupled receptor, which suffers a defective parking ubiq-uitination in autosomal recessive Parkinson’s disease promoting its endoplasmic reticulum aggregation and stress, neurotoxicity and neuronal death (Takahashi and Imai, 2003). Interestingly, we have demonstrated previously that GPR37 heteromerizes with adenosine A2A receptor (A2AR) in the striatum (Morató et al., 2017; Sokolina et al., 2017). In addition, we also report-ed some functional consequences of this direct interaction, whereby GPR37 deletion enhanced striatal A2AR cell surface expression with a concomitant increase in A2AR agonist-me-diated cAMP accumulation (Morató et al., 2017); accordingly, an enhancement of A2AR agonist-induced catalepsy and antag-onist-induced locomotor activity was observed upon GPR37 deletion (Morató et al., 2017). Overall, it has been hypothesized that GPR37 might hold a chaperone-like activity controlling A2AR cell surface targeting and function. However, the precise physiological function of GPR37 still is unidentified. The cur-rent findings now provide additional evidence for the role of GPR37 as a repressor of A2AR function. Thus, while chronic A2AR antagonist treatment (i.e., SCH58261, 1 mg/kg per day, intraperitoneal administration, 10 days) of mice lacking GPR37 did not affect the striatum-dependent cued leing, it en-hanced locomotor sensitization (Morató et al., 2019). Moreover, chronic A2AR blockade boosted striatal long-term depression (LTD) in corticostriatal synapses of GPR37-/- but not of wild type mice; this observation correlated well with the adenosin-ergic neurochemical modifications present in GPR37-/- mice, namely an increased density of A2AR and decreased levels of adenosine (Morató et al., 2019). Overall, GPR37 emerged as key contestant controlling A2AR function particularly upon chronic A2AR blockade, thus delineating A2AR-dependent long-term plastic changes in corticostriatal synapses.