OR51E2 is an olfactory receptor that functions as a G protein-coupled receptor with diverse physiological roles beyond olfaction 1. The receptor is activated by multiple ligands including short-chain fatty acids (acetate, propionate), β-ionone (a terpenoid), and palmitic acid 234. Mechanistically, OR51E2 activation leads to G protein signaling, elevated intracellular calcium and cAMP levels, and activation of protein kinases PKA and MAPK 2. Structural studies reveal that ligands bind within an occluded pocket, with propionate-induced conformational changes in extracellular loop 3 driving receptor activation 2. OR51E2 demonstrates significant disease relevance in cancer biology, where it functions as a tumor suppressor in colorectal and prostate cancers 35. In colorectal cancer, OR51E2 expression is reduced due to m6A modification affecting mRNA stability, and β-ionone treatment suppresses tumor growth by inhibiting MEK/ERK signaling 3. In prostate cancer, reduced OR51E2 expression correlates with worse patient prognosis and increased cancer aggressiveness through STAT3 pathway modulation 5. Additionally, OR51E2 is expressed in tumor-associated macrophages where palmitic acid binding enhances their protumor phenotype 4. The receptor also functions in gastrointestinal enterochromaffin cells, responding to bacterial metabolites 6.