MFSD2B is a sphingosine-1-phosphate (S1P) transporter that mediates S1P export from red blood cells and platelets 1. As a major facilitator superfamily transporter, MFSD2B functions as a proton-gradient-dependent uniporter that recognizes multiple S1P species and can also mediate S1P import 2. Structurally, S1P binds deeply within the C-domain with its phosphate group coordinated by polar residues, and translocation occurs via a TM2/TM11 lateral opening 2. Physiologically, MFSD2B contributes approximately half of circulating plasma S1P levels 1. In erythrocytes, MFSD2B-mediated S1P export is critical for red blood cell morphology and adaptation to hypoxia 3. In platelets, MFSD2B-derived S1P is essential for platelet aggregation and thrombus formation 3, while also providing cardioprotection during myocardial infarction 4. MFSD2B also functions in cardiomyocytes, where intracellular S1P accumulation (via reduced MFSD2B activity) protects against hypertension-induced cardiac remodeling by inhibiting L-type calcium channels through protein phosphatase 2A activation 5. In longevity individuals, reduced MFSD2B expression in erythrocytes elevates intracellular S1P, promoting metabolic reprogramming and enhanced antioxidative capacity 6.