{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have identified MFSD2B, a member of the major facilitator superfamily, as a critical exporter of sphingosine‐1‐phosphate (S1P) in hematopoietic cells. Investigations in erythroid cell‐derived models have shown that MFSD2B mediates the export of S1P into the bloodstream, with gene knockout experiments leading to markedly reduced S1P release. In addition, a closely related protein, MFSD2A, which shares a conserved 12-transmembrane domain structure, has been characterized in various tissues—its expression being modulated under metabolic stresses such as fasting and cold-induced thermogenesis—pointing to a broader functional family involved in lipid transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nDissecting the mechanistic details reveals that MFSD2B utilizes a proton gradient to drive the export of S1P. In erythrocytes and platelets alike, resting cells accumulate S1P intracellularly; however, upon activation, S1P is mobilized to the plasma membrane where MFSD2B functions to export it. Key residues within MFSD2B, such as D95 and T157, are indispensable for this transport activity. In platelets, loss of MFSD2B leads not only to sphingolipid accumulation but also to significant alterations in morphology and function, which manifest as impaired thrombus formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n\nThe physiological impact of MFSD2B-mediated S1P export is profound, extending to the integrity of blood vessels and cardioprotection. Studies combining deletion of MFSD2B with other S1P transporters, such as SPNS2, demonstrate that S1P export is essential for proper vascular development and homeostasis—with deficiencies resulting in severe hemorrhage and compromised vascular barriers. Moreover, platelet-derived S1P has been shown to exert cardioprotective effects during acute myocardial infarction, suggesting that MFSD2B and its regulated S1P release represent promising targets for therapeutic intervention in thrombotic and cardiovascular disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Martin Angers, Marc Uldry, Dong Kong, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Erythrocytes efficiently utilize exogenous sphingosines for S1P synthesis and export via Mfsd2b."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.012941"}], "href": "https://doi.org/10.1074/jbc.RA120.012941"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33334894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33334894"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Madhuvanthi Chandrakanthan, Toan Quoc Nguyen, Zafrul Hasan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of Mfsd2b impairs thrombotic functions of platelets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-22642-x"}], "href": "https://doi.org/10.1038/s41467-021-22642-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33863882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33863882"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Thanh Nha Uyen Le, Toan Q Nguyen, Pazhanichamy Kalailingam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2022.111208"}], "href": "https://doi.org/10.1016/j.celrep.2022.111208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35977478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35977478"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Amin Polzin, Lisa Dannenberg, Marcel Benkhoff, et al. 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