GPR156 (G protein-coupled receptor 156), is a human gene which encodes a G protein-coupled receptor belonging to metabotropic glutamate receptor subfamily.^[5] By sequence homology, this gene was proposed as being a possible GABA_B receptor subunit, however when expressed in cells alone or with other GABA_B subunits, no response to GABA_B ligands could be detected. In vitro studies on GPR156 constitutive activity revealed a high level of basal activation and coupling with members of the Gi/Go heterotrimeric G protein family.^[6] In 2021, an article was reported that GPR156 modulates hair cell orientation in the cochlea.^[7] Also, it was proposed that GPR156 is related to congenital hearing loss.^[8] GPR156 in complex with any of the Gi/o heterotrimers regulates the hair cell orientation.^[9] In 2024, molecular structures of G-free and Go-bound GPR156 were characterized by using cryogenic electron microscopy.^[10]

Among class C GPCR family members, GPR156 is unique because it lacks a large extracellular domain. Structural analyses revealed that the asymmetric binding of Go-protein to GPR156 triggers conformational change of its cytoplasmic face without altering dimer interface.^[10]  Although the inactive class C GPCRs undergo rearrangement of their dimeric interface, the agonist- and/or the positive allosteric modulator-bound class C GPCRs retain their dimeric interface upon G-protein binding. Thus, the G-free GPR156 is likely to represent an active state.^[10] Structural and functional analyses suggest that abundant endogenous phospholipids, receptor dimerization, and the G-protein binding-induced conformational change of the cytoplasmic face are the primary reasons for constitutive activation of GPR156.^[10] Phosphatidylglycerol further stimulates the activity of GPR156, which suggests the environmental changes of the phospholipid composition may regulate the GPR156 activity.^[10]