# Functional diversity of BAI1 (ADGRB1): From angiostasis to synaptic remodeling and disease therapeutics

## TL;DR

This paper reviews the diverse roles of BAI1 in processes like angiogenesis, tumor suppression, and brain development, highlighting its potential in disease therapeutics.

## Contribution

The paper systematically integrates current knowledge on BAI1's genomic regulation, isoform diversity, and biological functions.

## Key findings

- BAI1 is regulated by epigenetic factors like MBD2, EZH2, and p53, leading to distinct isoforms.
- BAI1 and its extracellular domains inhibit angiogenesis, suppress tumors, and modulate immune responses.
- BAI1 is involved in synaptic plasticity and is linked to neuropsychiatric disorders.

## Abstract

Brain-specific angiogenesis inhibitor 1 (BAI1/ADGRB1), a member of the adhesion G protein-coupled receptor (ADGR) family, is regulated at the transcriptional level through epigenetic mechanisms (e.g., MBD2, EZH2, and p53) and alternative promoters, resulting in molecularly distinct isoforms via differential promoters usage (e.g., intron 17-derived variants) and post-translational processing (e.g., matrix metalloproteinase 14 [MMP-14]-mediated Vstat40 release). In cellular and animal studies, both the full-length BAI1 and its proteolytically released extracellular domains have been showed to exhibit multifaceted bioactivity, including inhibition of angiogenesis, suppression of tumor progression, and modulation of immune responses via interactions with CD36, integrins, lipopolysaccharide (LPS), and phosphatidylserine (PtdSer). Furthermore, BAI1 plays crucial roles in neurodevelopmental processes such as synaptic plasticity, neuronal differentiation, and cellular debris clearance, with emerging links to neuropsychiatric disorders. Despite significant advances, critical gaps remain in understanding isoform-specific functions and activation mechanisms across different tissues. This review systematically integrates current knowledge on BAI1, focusing on its genomic regulatory mechanisms, structural isoform diversity, and multidimensional biological functions. It also underscores the need to explore the translational potential of BAI1 in oncology, neurodegenerative diseases, and immune dysregulation, which is essential for advancing our understanding of this complex receptor and its therapeutic applications.

Health sciences; Natural sciences; Biological sciences; Biochemistry; Physiology