BAI2

BAI2 Full Name

brain-specific angiogenesis inhibitor 2

BAI2 Introduction

BAI2, also known as brain-specific angiogenesis inhibitor 2 or ADGRB2 (adhesion G protein-coupled receptor B2), is an adhesion G protein-coupled receptor (aGPCR) encoded by the ADGRB2 gene on chromosome 1p35.2. Unlike conventional GPCRs that primarily respond to soluble ligands, BAI2 contains a large extracellular N-terminal region, a GPCR autoproteolysis-inducing (GAIN) domain, and a seven-transmembrane receptor domain, enabling it to participate in cell adhesion and receptor-mediated signaling. BAI2 shows prominent expression in the nervous system, particularly in brain regions involved in neuronal communication, and was originally characterized as a brain-associated inhibitor of angiogenesis. Its biological relevance is therefore broader than its original angiogenesis-related name suggests: BAI2 is increasingly viewed as a signaling and synaptic adhesion receptor connecting extracellular interactions with intracellular pathways.

For researchers investigating BAI2, one of the key challenges is that its functions are still less completely characterized than those of other BAI family members. Current evidence indicates that proteolytic processing of the receptor can regulate its activity, while BAI2 signaling can activate the NFAT pathway through G-protein-dependent mechanisms. More recent neuroscience research has strengthened the link between BAI2 and neuronal connectivity: ADGRB2 is enriched at postsynaptic sites in the hippocampus, and loss of BAI2 reduces glutamatergic synapse density and mushroom-shaped dendritic spines during development. These findings suggest that BAI2 may contribute to synaptic organization, neuronal signaling, and the maintenance of excitatory neural circuits, making it a potentially useful target for studies of cell adhesion, GPCR signaling, synapse biology, and brain function.

BAI2 is also attracting attention because altered signaling or genetic variation may connect this receptor with neurological and psychiatric disease mechanisms. Studies have associated BAI2-related variants with neurodevelopmental and psychiatric phenotypes, while a rare gain-of-function mutation has been implicated in a human spastic paraparesis condition, highlighting the potential consequences of excessive receptor signaling. BAI2 has additionally been investigated in the context of brain angiogenesis and tumor biology, including its proposed role as an anti-angiogenic factor. However, many disease associations remain mechanistic or observational rather than establishing BAI2 as a direct disease-causing target. For drug discovery and translational research, this distinction is important: BAI2 currently represents an emerging target whose value may lie in understanding how adhesion GPCR signaling, synaptic development, angiogenesis, and neurological disease intersect, rather than being regarded as an already validated therapeutic target.

Alternate Names for BAI2

BAI2; brain-specific angiogenesis inhibitor 2;

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• 1.Alsharif HA, Bhatnagar S. Cell-Specific Functions of the BAI/ADGRB Subfamily of Adhesion G-Protein Coupled Receptors. Compr Physiol. 2025, 15(6):e70068.
  2.Meyer CM,et al.; Regulation of hippocampal excitatory synapse development by the adhesion G-protein coupled receptor Brain-specific angiogenesis inhibitor 2 (BAI2/ADGRB2). bioRxiv [Preprint]. 2025, 2025.02.02.636169.