{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ADGRB3 (also known as Brain‐specific angiogenesis inhibitor 3 or BAI3) is an adhesion G protein–coupled receptor that plays multifaceted roles in both brain and peripheral tissues. In the central nervous system, ADGRB3 is highly expressed during development and acts as a key regulator of synapse formation, remodeling, and dendritic arborization. It binds secreted C1q‐like proteins to modulate excitatory synapse density and to refine neural circuit connectivity – functions that are underscored by its association with disorganized symptoms in psychiatric conditions and neurodevelopmental deficits when disrupted."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the cerebellum, ADGRB3 mediates the “winner‐take‐all” process during synapse elimination by transducing anterograde signals from climbing fibers, thereby contributing to motor learning."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Beyond the nervous system, ADGRB3 is essential for myoblast fusion and normal muscle development by engaging intracellular effectors such as ELMO proteins; loss of ADGRB3 function in muscle progenitors impairs fusion and subsequent regeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, the receptor’s extensive extracellular region undergoes autoproteolytic cleavage within its GAIN domain to expose a tethered agonist—a mechanism that is critical for its regulated, context‐dependent signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In addition to its classical roles in neuronal and muscular development, ADGRB3 has been implicated in the regulation of vascular and metabolic processes. Genetic variation at the ADGRB3 locus has been associated with altered plasma levels of coagulation factors and insulin secretion, suggesting that ADGRB3 signaling may help modulate angiogenesis and metabolic homeostasis"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": ", and variants in ADGRB3 are linked with body mass index in population studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Aberrant ADGRB3 expression has also emerged as a diagnostic marker in small‐cell lung carcinoma, where its unusual subcellular localization may reflect altered receptor processing in tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Furthermore, rare disruptions and copy number alterations affecting ADGRB3 have been linked to neurodevelopmental disorders—including intellectual disability, ataxia, and behavioral abnormalities"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and even co‐segregate with connective tissue and cranial anomalies in clinical cohorts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Collectively, these findings reveal that ADGRB3 functions as a dynamic cell–cell adhesion and signaling receptor whose diverse activities are critical for proper synaptic connectivity, muscle formation, vascular regulation, and metabolic as well as tumor‐related processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Terracciano, S Sanna, M Uda, et al. 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