GPR12 is a brain-specific orphan G protein-coupled receptor that exhibits constitutive activity and plays important roles in central nervous system function and cancer regulation 1 2. The receptor demonstrates high constitutive activation of adenylyl cyclase, stimulating cAMP production through Gs protein coupling, with structural features including extracellular loop 2 occupying the orthosteric binding pocket contributing to this intrinsic activity 3. GPR12 also engages Gi/Go pathways, which counteract cAMP increases driven by Gs activation 4. Sphingosine-1-phosphate (S1P) and dihydrosphingosine-1-phosphate have been identified as potential endogenous ligands that can modulate receptor activity 4. The receptor serves as a therapeutic target for neurological disorders including Alzheimer's disease, Parkinson's disease, and schizophrenia 1 5. Cannabidiol acts as an inverse agonist for GPR12, highlighting potential therapeutic applications 6. In cancer contexts, GPR12 functions as a tumor suppressor by inhibiting cell migration through epithelial-to-mesenchymal transition modulation and promoting apoptosis via caspase-7 activation in esophageal and hypopharyngeal cancers 2. Additionally, GPR12 expression is regulated by fluid shear stress in endothelial cells, suggesting vascular functions 7.