ADORA2B encodes the adenosine A2b receptor, a G protein-coupled receptor with the lowest affinity for adenosine among the four adenosine receptors 1. The receptor mediates adenylyl cyclase activation through G protein signaling and is localized to chromosome 17 2. ADORA2B expression is significantly elevated under hypoxic conditions and in diseased tissues compared to normal tissue 1 3. The receptor plays critical roles in immune regulation, with hypoxia-inducible factor 1-α (HIF1A) upregulating ADORA2B expression on alternatively activated macrophages, contributing to pulmonary fibrosis through IL-6 production 4. In cancer contexts, ADORA2B promotes tumor progression through multiple mechanisms including enhanced cell proliferation and migration 5, regulation of epithelial-mesenchymal transition via the cAMP/PKA/Snail pathway 3, and creation of an immunosuppressive tumor microenvironment 1 3. The receptor also functions in cognitive processes, with ADORA2B knockout mice showing impaired hippocampus-dependent learning and memory through reduced C-FOS expression 6. Additionally, ADORA2B activation promotes penile rehabilitation in erectile dysfunction by alleviating hypoxia and fibrosis 7. These findings highlight ADORA2B as a potential therapeutic target across multiple pathological conditions.