HRH1 encodes the histamine H1 receptor, a G-protein-coupled receptor that mediates diverse physiological and pathological processes through histamine signaling 1. The receptor activates phospholipase C signaling pathways and regulates smooth muscle contraction and vascular permeability. In cancer, HRH1 exhibits immunosuppressive functions by promoting M2-like macrophage polarization and increasing VISTA expression, leading to T cell dysfunction and immunotherapy resistance 1. HRH1 also facilitates tumor progression in cholangiocarcinoma by promoting cell proliferation through Gαq signaling and enhancing angiogenesis 2. In pancreatic cancer, HRH1 downregulates MHC-I expression via cholesterol biosynthesis pathways, contributing to immune evasion 3. The receptor mediates pain signaling in endometriosis through histamine/HRH1/TRPV1 pathways and sensory neuron sensitization 4. HRH1 inverse agonists show therapeutic potential in osteoarthritis by activating FOXO3 and reducing inflammation 5. Additionally, HRH1 promotes γδT17 cell differentiation in psoriasis via Wnt signaling activation 6. Genetic polymorphisms in HRH1, particularly rs901865, influence antihistamine treatment responses and side effect severity 7. These findings highlight HRH1's multifaceted roles in immunity, inflammation, and disease pathogenesis.