TPRA1 (transmembrane protein adipocyte associated 1) is a G protein-coupled receptor that functions as a membrane-localized signaling protein with diverse roles in viral infection, developmental signaling, and inflammatory disease. Mechanistically, TPRA1 operates through multiple pathways: it serves as a novel receptor for oncolytic virus M1, facilitating viral entry through both glycosylation-dependent attachment and receptor-mediated endocytosis 1. TPRA1 localizes to primary cilia upon Hedgehog stimulation, where it positively regulates Hedgehog signaling by coupling to Gαi proteins and suppressing cAMP production to prevent Gli3 repressor formation 2. Additionally, TPRA1 mediates functional membrane transport through interaction with Sjögren's syndrome-associated protein NA14, which regulates cell division during embryogenesis 3. Disease relevance spans multiple conditions: TPRA1 expression correlates with oncolytic virus sensitivity in cancer cells, positioning it as a biomarker for patient selection in OVM-based therapy 1. Genetic-epigenetic interactions at TPRA1 associate with asthma pathogenesis 4, and synovial TPRA1 expression exhibits causal relationships with rheumatoid arthritis susceptibility 5. TPRA1 also functions as a sensory receptor for plant-derived coumarins that induce numbing orosensation 6. These findings establish TPRA1 as a multifunctional receptor with significant implications for oncology, inflammatory diseases, and sensory biology.