FFAR4 (GPR120) is a G protein-coupled receptor that functions as a sensor for long-chain fatty acids, particularly omega-3 unsaturated fatty acids 1. Upon ligand binding, FFAR4 associates with β-arrestin-2, which serves as an adapter protein coupling the receptor to downstream signaling pathways and mediating receptor endocytosis 2. FFAR4 activation triggers multiple physiological responses including anti-inflammatory effects through NLRP3 inflammasome inhibition and enhancement of systemic insulin sensitivity 3. In intestinal immunity, FFAR4 regulates CD4+ T cell IL-10 production to suppress colitis development 4. Additionally, FFAR4 on islet macrophages promotes IL-6 release, which enhances glucose-stimulated insulin secretion in lean mice, though this signaling is impaired in obesity and type 2 diabetes 5. In kidney disease, podocyte FFAR4 expression is abnormally reduced, and FFAR4 agonism protects against glomerular damage through CaMKKβ-AMPK pathway activation, mitigating cellular senescence and lipotoxicity 6. Clinical significance is emerging as FFAR4 agonists show promise for metabolic and inflammatory disorders; however, enhanced FFAR4 signaling may paradoxically promote certain cancers 7.