P2RY11 encodes a G protein-coupled purinergic receptor that responds to extracellular ATP and ADP, coupling to both phospholipase C and adenylyl cyclase signaling pathways 1. Unlike other P2Y receptors, P2RY11 is uniquely absent from rodent genomes and contains an intron within its coding sequence, limiting mechanistic studies 1. P2RY11 functions primarily in immune regulation, with cell-type-specific effects on inflammatory responses 2. The receptor is expressed in T lymphocytes and intestinal epithelial cells, where it mediates ATP-induced calcium signaling and cellular responses 34. In respiratory epithelium, P2RY11 activation via lipoxin A4-stimulated ATP release restores airway surface liquid height and promotes epithelial repair through phospholipase C-dependent calcium mobilization and cAMP signaling 5. P2RY11 also couples extracellular ATP to cellular senescence through ER-to-mitochondria calcium transfer and reactive oxygen species production, with implications for cancer cell proliferation 6. Clinically, P2RY11 polymorphisms associate with narcolepsy type 1, an autoimmune disorder affecting hypocretin neurons, with reduced P2Y11 protein levels in T lymphocytes correlating with increased nocturnal sleep fragmentation 74. These findings suggest P2RY11 roles in immune surveillance, epithelial barrier function, and sleep-wake homeostasis.