Cell-Specific Functions of the BAI/ADGRB Subfamily of Adhesion G-Protein Coupled Receptors

G protein-coupled receptors (GPCRs) are key regulators of various physiological processes and remain the most targeted class of proteins in drug development. Although significant progress has been made in understanding many GPCR families, adhesion-type GPCRs (aGPCRs) are among the least characterized. aGPCRs are distinguished by their large extracellular regions that contain multiple functional domains, an autoproteolytic GPCR proteolysis site (GPS), and intracellular motifs that support downstream signaling. Within this family, the brain-specific angiogenesis inhibitor (BAI) subfamily-comprising BAI1 (ADGRB1), BAI2 (ADGRB2), and BAI3 (ADGRB3)-has become a key player in numerous biological processes, including synaptogenesis, synaptic plasticity, spinogenesis, apoptotic cell clearance, myoblast fusion, vascular development, cellular secretion, and behavioral regulation. Genetic polymorphisms and functional disruptions in BAI receptors have been associated with a range of conditions such as cancer, neurodevelopmental disorders, and metabolic syndromes. Although recent research has started to uncover the roles of BAI receptors in energy balance and metabolism, their functions in glucose homeostasis and metabolic disease are still not fully understood. This review summarizes the current knowledge of the roles of BAI1, BAI2, and BAI3 across multiple physiological systems, offering new perspectives on how this receptor subfamily may influence systemic glucose regulation and highlighting its potential as a therapeutic target for metabolic disorders.