{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Afamin (AFM) is a liver‐derived glycoprotein best known for its ability to bind and transport hydrophobic molecules such as vitamin E in various body fluids, including plasma, follicular fluid, cerebrospinal fluid, and across the blood–brain barrier."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition to its role as a transport protein, recent structural and functional studies have revealed that afamin acts as an extracellular chaperone capable of solubilizing poorly soluble, acylated Wnt proteins, thereby potentially affecting long‐range signaling processes in the central nervous system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Beyond its classical transport functions, serum afamin levels have been associated with metabolic regulation; elevated concentrations are linked with insulin resistance, metabolic syndrome, and altered lipid profiles, while changes in afamin have also been observed in conditions such as alcoholic liver cirrhosis where declining levels correlate with disease severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Afamin is also emerging as a potential biomarker in reproductive and oncologic settings. During pregnancy, afamin concentrations progressively rise and have been linked to pre‐eclampsia risk when combined with vascular measures, whereas reduced or dysregulated afamin levels have been reported in ovarian cancer, suggesting its utility in diagnosis and monitoring."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " Moreover, studies in bone physiology indicate that afamin, secreted by osteoclasts, promotes the migration of preosteoblasts through Akt‐mediated pathways, implicating it in the coupling of bone resorption and formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, afamin overexpression in thyroid cancer models has been linked to enhanced glycolytic activity via the upregulation of key enzymes, suggesting a role in modulating cancer cell metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings highlight afamin’s multifunctional nature as a binding/transport protein, an extracellular chaperone for lipid‐modified signaling molecules, a metabolic biomarker, and a modulator of cellular processes in diverse physiological and pathological settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andreas F Voegele, Lidija Jerković, Bernd Wellenzohn, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Afamin is synthesized by cerebrovascular endothelial cells and mediates alpha-tocopherol transport across an in vitro model of the blood-brain barrier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2008.05796.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2008.05796.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19046407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19046407"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Andreas Naschberger, Andrew Orry, Stefan Lechner, et al. 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