Gpr61 is an orphan G protein-coupled receptor (GPCR) related to biogenic amine receptors [1]. It couples to Gαs and shows constitutive activity, and is thought to be involved in regulating cAMP levels [4]. Its association with appetite-related phenotypes makes it a potential druggable target for metabolism and body-weight-related disorders like obesity and cachexia [1].

Recent studies have reported the discovery of a potent and selective small-molecule inverse agonist against GPR61, along with the structural elucidation of its allosteric binding site and mode of action, which provides a framework for further functional studies [1]. Prenatal exposure to air pollutants may affect GPR61 methylation in cord blood, suggesting a potential link between environmental factors and GPR61-related functions [2]. Additionally, GPR61 has been associated with the regulation of birth weight, as both maternal and neonatal GPR61 methylation levels are affected by weather factors, and neonatal GPR61 methylation may mediate the effects of relative humidity and daily temperature range on birth weight [3].

In conclusion, Gpr61 is a significant orphan GPCR with potential implications in metabolism-related diseases and response to environmental factors. The discovery of its inverse agonist and the understanding of its methylation-related environmental responses contribute to the knowledge of its role in biological processes and potential disease-related mechanisms.