ADORA3 is a G protein-coupled adenosine receptor that inhibits adenylyl cyclase signaling and is widely expressed across tissues, particularly in the brain and intestinal tract. The receptor participates in diverse physiological processes including inflammatory responses, cell migration, mast cell degranulation, and heart rate regulation. ADORA3 has emerged as a therapeutic target in multiple disease contexts. In vascular dementia, ADORA3 antagonism promotes microglial phagocytosis of myelin debris via the cAMP/PKA/p-CREB pathway, alleviating white matter injury and cognitive impairment 1. In ulcerative colitis, ADORA3 activation enhances goblet cell differentiation through HMGCS2-mediated ketogenesis, mitigating disease severity 2. Following intracerebral hemorrhage, ADORA3 inhibition accelerates hematoma resolution by promoting microglial erythrophagocytosis and reducing neuroinflammation 3. In intracranial aneurysms, elevated ADORA3 expression correlates with vascular smooth muscle cell autophagy and shows promise as a diagnostic biomarker 4. ADORA3 genetic variants also influence methotrexate efficacy in juvenile idiopathic arthritis, with certain polymorphisms associated with improved response and reduced gastrointestinal toxicity 5. Clinical adenosine receptor modulators including adenosine agonists and theophylline derivatives target this pathway, with selective ADORA3 antagonists like MRS1523 and MRS1191 demonstrating therapeutic benefit in preclinical models.