ADORA1 encodes the adenosine A1 receptor, a G protein-coupled receptor that mediates adenosine signaling through inhibition of adenylyl cyclase via GNAI2 1. This receptor functions across multiple physiological systems with distinct roles in health and disease. In the nervous system, ADORA1 plays critical roles in sleep homeostasis, where neuronal A1 receptors facilitate slow-wave activity during sleep through adenosine accumulation in a neuronal-glial circuit 2. However, ADORA1 upregulation is pathologically implicated in Alzheimer's disease, where tau pathology increases neuronal A1R expression via miR-133a-3p regulation, promoting astrocyte activation and neurodegeneration 3. A loss-of-function ADORA1 mutation (p.Gly279Ser) causes early-onset parkinsonism and cognitive dysfunction, likely through disrupted interaction with dopamine D1 receptors 4. In cancer immunology, ADORA1 deletion suppresses melanoma cell growth but paradoxically promotes immune evasion by upregulating PD-L1 via ATF3, which can be overcome with PD-1 checkpoint inhibition 5. ADORA1 also mediates stress-induced anxiety through purine metabolic dysfunction in CD4+ T cells, where CD4-derived xanthine activates oligodendrocytes via A1 receptors 6. Additionally, ADORA1 expression is significantly elevated in epicardial adipose tissue and associates with cardiac physiology and coronary artery disease pathophysiology 7.