HRH4 encodes the histamine receptor H4, a G protein-coupled receptor primarily expressed in immune cells including mast cells, eosinophils, basophils, dendritic cells, and neutrophils 1. The receptor plays a crucial role in immune and inflammatory responses by mediating chemotaxis of immune cells to sites of inflammation and injury in response to histamine 1. Upon ligand binding, HRH4 undergoes conformational changes that trigger signaling via G(i) proteins, leading to decreased intracellular cAMP levels through adenylate cyclase inhibition. The receptor influences the release of proinflammatory cytokines including TNF, CCL4, IL-6, and IFN-gamma. Genetic polymorphisms in HRH4, particularly rs11665084 (Ala138Val) and rs11662595 (His206Arg), show population variability and have been associated with infection-induced asthma susceptibility 23. HRH4 expression is dysregulated in various cancers, with deletion and downregulation observed in gastric carcinomas correlating with tumor progression 4. The receptor also functions in reproductive tissues, inhibiting steroidogenesis and proliferation in Leydig cells 5, and shows elevated expression in endometriosis alongside increased histamine levels 6. Additionally, HRH4 is upregulated in breast cancer, particularly in triple-negative and HER2+ subtypes 7.