ADGRF1 (adhesion G protein-coupled receptor F1) is an adhesion G protein-coupled receptor that serves as the specific receptor for synaptamide (N-docosahexaenoylethanolamine), an omega-3 fatty acid metabolite highly enriched in the brain 1. The receptor functions through tethered agonism, where its stalk region acts as an intrinsic tethered agonist by forming extensive interactions with the transmembrane domain 2. ADGRF1 primarily couples to Gαs proteins, activating adenylate cyclase and increasing cAMP production, which leads to phosphorylation of protein kinase A and CREB 1. This signaling pathway promotes neurogenesis, neurite outgrowth, and synaptogenesis in developing neurons while suppressing neuroinflammatory responses 1. In cancer contexts, ADGRF1 demonstrates complex roles - it promotes tumorigenesis and chemoresistance in HER2-positive breast cancer by inducing cellular quiescence 3, but can switch to tumor-suppressive function when interacting with laminin-111 4. In hepatic metabolism, ADGRF1 regulates lipid accumulation through control of stearoyl-CoA desaturase 1 expression, with decreased expression serving as a protective mechanism against fatty liver disease 5. The receptor's expression is elevated in various cancers and associated with poor prognosis 6.