P2RY14 is a G protein-coupled purinergic receptor that binds UDP-glucose and other UDP-sugars, but not ATP or ADP 1. It functions as a damage-associated molecular pattern (DAMP) receptor enriched in hepatic stellate cells, where UDP-glucose released from dying hepatocytes activates P2Y14-dependent ERK and YAP signaling to promote fibrogenesis 1. In immune contexts, P2Y14 activation by UDP-glucose prolongs eosinophil lifespan and promotes ERK1/2-mediated gene transcription, aggravating intestinal inflammation in ulcerative colitis 2. P2RY14 also signals via Gi proteins to regulate intracellular cAMP levels, controlling Schwann cell precursor self-renewal and neurofibroma initiation in neurofibromatosis type 1 3. Clinically, P2RY14 expression correlates with prognosis across multiple malignancies: elevated expression associates with better outcomes in ovarian cancer through modulation of immune infiltration and checkpoint markers 4, while reduced expression characterizes esophageal adenocarcinoma progression from Barrett's esophagus 5. P2RY14 was identified as a candidate gene in colorectal cancer liver metastasis 6, aging-related acute respiratory distress syndrome 7, and irritable bowel syndrome susceptibility 8, suggesting its broad involvement in inflammation, fibrosis, and tumor biology.