Affinage

PLTP

Phospholipid transfer protein · UniProt P55058

Length
493 aa
Mass
54.7 kDa
Annotated
2026-04-28
90 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLTP is a secreted lipid transfer glycoprotein that shuttles phospholipids and alpha-tocopherol between lipoproteins and across tissue barriers, functioning as a central regulator of HDL remodeling, hepatic VLDL assembly, brain vitamin E homeostasis, and innate/adaptive immune signaling. Its banana-shaped, two-domain architecture contains an N-terminal lipid-binding pocket essential for phospholipid transfer—a prerequisite for HDL conversion into larger fusion particles and prebeta-HDL generation—and a C-terminal pocket that mediates HDL association via apoA-I (residues 27–141) and apoE, with PLTP circulating as a high-activity (~160 kDa, apoE-associated) and a low-activity (~520 kDa, apoA-I-associated) form (PMID:10357844, PMID:11123937, PMID:9469594, PMID:11854286, PMID:29883800). Beyond lipid transfer, PLTP activates STAT3 and suppresses NF-κB in macrophages through an ABCA1-dependent, lipid-transfer-independent signaling mechanism, modulates CD4+ T-helper cell polarization, and in hepatocellular carcinoma forms a ternary complex with AURKA and NF-κB p65 to drive pro-inflammatory cytokine expression (PMID:21782857, PMID:26320740, PMID:41391040). PLTP is transcriptionally regulated by LXR, FXR, and p53, and its expression is epigenetically silenced by DNMT3B-mediated promoter hypermethylation in diabetic retinopathy, where it promotes endothelial function via AKT/GSK3β signaling (PMID:12454263, PMID:36309086, PMID:40380281).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1995 High

    Establishing that phospholipid transfer and HDL conversion are intrinsic activities of the PLTP protein resolved whether these were separable plasma functions or properties of a single gene product.

    Evidence Recombinant human/mouse PLTP expressed in BHK cells reconstituted both activities in vitro

    PMID:7654777

    Open questions at the time
    • Structural basis for dual activity unknown
    • Relationship between phospholipid transfer and HDL conversion not yet causally ordered
  2. 1998 High

    Mapping the PLTP-binding domain on apoA-I to residues 27–141 identified the molecular interface through which PLTP engages its principal HDL-associated apolipoprotein partner.

    Evidence Solid-phase binding, ELISA, affinity chromatography, and monoclonal antibody epitope mapping

    PMID:9469594

    Open questions at the time
    • Reciprocal mapping of the apoA-I-binding site on PLTP not determined
    • Structural resolution of the PLTP–apoA-I complex lacking
  3. 1999 High

    Homology modeling and site-directed mutagenesis established PLTP's two-domain BPI-like architecture and demonstrated that both N- and C-terminal lipid-binding pockets are functionally required, with the N-terminal pocket driving phospholipid transfer and the C-terminal pocket mediating HDL binding.

    Evidence Structure-guided mutagenesis of lipid-pocket residues in HeLa-expressed PLTP, solid-phase HDL-binding assay

    PMID:10357844

    Open questions at the time
    • No crystal structure of PLTP itself
    • Contribution of the C-terminal pocket to transfer vs. binding not fully delineated
  4. 1999 High

    Discovery of an intrinsic serine esterase-type protease activity in PLTP that cleaves apoA-I at Ala196–Thr197 revealed an unexpected catalytic function beyond lipid transfer.

    Evidence Mass spectrometry, N-terminal sequencing, and protease inhibitor studies on recombinant PLTP from multiple expression systems

    PMID:10191289

    Open questions at the time
    • Physiological significance of apoA-I cleavage in vivo undetermined
    • Active-site residues responsible for protease activity not identified
  5. 2000 High

    Demonstrating that phospholipid transfer is a prerequisite for HDL conversion causally ordered PLTP's two activities: lipid transfer must occur before apoA-I release and prebeta-HDL generation.

    Evidence Chemical modification and N-terminal pocket mutants abolished both transfer and HDL conversion in parallel

    PMID:11123937

    Open questions at the time
    • Kinetic mechanism of coupled transfer-to-conversion not resolved
    • Whether intermediate lipid species are required not tested
  6. 2002 High

    Resolution of two circulating PLTP forms—a high-activity ~160 kDa apoE-associated form and a low-activity ~520 kDa apoA-I-associated form—explained the long-standing discrepancy between PLTP mass and activity measurements in plasma.

    Evidence Heparin-Sepharose and gel filtration chromatography, immunoaffinity separation with anti-apoE/anti-apoA-I

    PMID:11854286 PMID:12810820

    Open questions at the time
    • What converts HA-PLTP to LA-PLTP is unknown
    • Whether the two forms have distinct tissue origins not established
  7. 2002 High

    Identification of functional LXR and FXR response elements in the PLTP promoter placed PLTP under direct nuclear receptor transcriptional control, connecting its expression to cholesterol/bile acid sensing.

    Evidence Microarray, Northern blot, and promoter-reporter assays in human cells

    PMID:12454263

    Open questions at the time
    • Tissue-specific transcriptional regulation not fully characterized
    • Relative contribution of LXR vs. FXR in different tissues unknown
  8. 2004 High

    PLTP-knockout mice revealed a non-redundant role for PLTP in brain alpha-tocopherol delivery, with deficiency causing vitamin E depletion, oxidative stress, and behavioral abnormalities.

    Evidence PLTP-KO mouse model with alpha-tocopherol quantification, oxidative stress markers, and elevated plus-maze testing

    PMID:15576481

    Open questions at the time
    • Whether PLTP transfers vitamin E across the BBB directly or via lipoproteins not resolved
    • CNS cell types responsible for PLTP-mediated vitamin E transport not identified
  9. 2008 High

    In vivo studies using transfer-inactive PLTP mutant mice and PLTP transgenic mice established that phospholipid transfer activity is required for PLTP's pro-atherogenic effects including stimulation of hepatic VLDL secretion, impairment of reverse cholesterol transport, and atherosclerotic lesion progression.

    Evidence Transfer-inactive PLTP mutant transgenic mice, PLTP overexpression models, in vivo RCT assay, VLDL secretion, and atherosclerosis quantification

    PMID:18421000 PMID:18711210 PMID:19100548

    Open questions at the time
    • Molecular mechanism by which PLTP stimulates VLDL lipidation not resolved at the protein level
    • Whether transfer activity is also required for anti-inflammatory signaling not tested in vivo
  10. 2011 High

    Demonstration that both active and transfer-inactive PLTP activate STAT3 and suppress NF-κB in macrophages via ABCA1 uncovered a lipid-transfer-independent signaling function, separating PLTP's metabolic and immunomodulatory roles.

    Evidence Wild-type and M159E mutant PLTP treatment of THP1 and primary macrophages, ABCA1 siRNA and chemical inhibition, nuclear fractionation

    PMID:21782857

    Open questions at the time
    • How PLTP engages ABCA1 to activate STAT3 mechanistically unknown
    • Whether this signaling operates in vivo under physiological conditions not shown
  11. 2012 High

    Liver-specific PLTP rescue in PLTP-null mice showed that hepatic PLTP drives VLDL lipidation in the microsomal lumen and VLDL secretion without affecting HDL, establishing the liver as the primary tissue for PLTP's pro-atherogenic VLDL effects.

    Evidence Adenovirus-mediated liver-specific PLTP expression, hepatocyte microsomal VLDL lipidation assay

    PMID:22367708

    Open questions at the time
    • Whether PLTP acts on apoB directly or via an intermediary lipid donor in the ER lumen unknown
    • Contribution of intestinal PLTP to VLDL metabolism not addressed
  12. 2014 High

    In vivo loss- and gain-of-function experiments in lung established PLTP as an anti-inflammatory factor degraded by cathepsin G in COPD, bridging PLTP's lipid transfer function with innate immune regulation in the airway.

    Evidence PLTP siRNA and recombinant PLTP in mouse LPS lung injury model, cathepsin G cleavage of PLTP in BALF

    PMID:24532668

    Open questions at the time
    • Whether anti-inflammatory lung function is lipid-transfer-dependent or ABCA1/STAT3-dependent not distinguished
    • PLTP's substrate in the lung (LPS, surfactant phospholipids) not resolved
  13. 2014 Medium

    Linking PLTP deficiency to BBB breakdown via reduced tight junction proteins and oxidative stress—rescued by dietary vitamin E—provided a mechanistic chain from PLTP's vitamin E transfer activity to cerebrovascular integrity.

    Evidence Multiphoton imaging, Evans blue permeability assay, tight junction protein western blot, vitamin E dietary rescue in PLTP-KO mice

    PMID:24513285

    Open questions at the time
    • Direct measurement of PLTP-mediated vitamin E transport across BBB endothelium not performed
    • Whether tight junction loss is a direct or secondary consequence of oxidative stress not resolved
  14. 2015 Medium

    PLTP deficiency shifted CD4+ T-helper polarization toward Th2 and reduced IL-18, establishing PLTP as a modulator of adaptive immunity beyond its known innate immune roles.

    Evidence PLTP-KO mouse contact hypersensitivity model, flow cytometry for T-cell subsets, cytokine measurements

    PMID:26320740

    Open questions at the time
    • Whether effect on Th polarization is cell-autonomous or mediated by accessory cell lipid changes not resolved
    • Molecular mechanism linking PLTP to IL-18 production unknown
  15. 2018 Medium

    Electron microscopy visualization of PLTP's banana-shaped structure and its ternary complex with HDL and LDL provided the first direct structural basis for the shuttle transfer mechanism between lipoproteins.

    Evidence Single-particle EM analysis of PLTP and PLTP–lipoprotein complexes

    PMID:29883800

    Open questions at the time
    • Atomic-resolution structure not available
    • Whether the ternary complex is an obligate intermediate or one of multiple transfer modes not established
  16. 2020 Medium

    Identification of PLTP as a batokine secreted by brown adipose tissue that improves systemic glucose tolerance through bile acid-mediated interorgan signaling expanded PLTP's metabolic role beyond lipoprotein metabolism.

    Evidence Proteomics of human thermogenic adipocytes, BAT-specific PLTP overexpression mice, bile acid measurements, glucose tolerance tests

    PMID:32672883

    Open questions at the time
    • Mechanism by which PLTP increases bile acid levels not determined
    • Whether BAT-derived PLTP acts on hepatic VLDL secretion not tested
  17. 2022 Medium

    Establishing PLTP as a direct p53 transcriptional target that suppresses colony formation and regulates ferroptosis sensitivity connected PLTP to tumor suppression pathways beyond lipid metabolism.

    Evidence RNA-seq in lymphoblastoid cell lines with p53 hypomorphs, PLTP overexpression colony formation and ferroptosis assays

    PMID:36309086

    Open questions at the time
    • Mechanism of ferroptosis regulation by PLTP (lipid peroxidation vs. iron) not resolved
    • Whether PLTP tumor-suppressive function operates in vivo not tested
  18. 2025 Medium

    Discovery of a PLTP–AURKA–p65 ternary complex that activates NF-κB in hepatocellular carcinoma revealed that PLTP can also promote—not just suppress—NF-κB signaling in a context-dependent manner, driving M2 macrophage polarization and tumor-associated inflammation.

    Evidence Reciprocal co-IP, molecular docking, proteomics, PLTP overexpression in HCC cells and mouse tumor models

    PMID:41391040

    Open questions at the time
    • Apparent contradiction with anti-inflammatory NF-κB suppression in macrophages not reconciled
    • Whether AURKA kinase activity is required for the PLTP-mediated p65 activation not tested
    • Single-lab finding awaiting independent replication
  19. 2025 Medium

    Identification of DNMT3B-mediated promoter hypermethylation as a mechanism silencing PLTP in diabetic retinopathy, with downstream AKT/GSK3β signaling rescuing endothelial dysfunction, added an epigenetic regulatory layer to PLTP biology.

    Evidence DNMT3B siRNA, luciferase reporter, PLTP overexpression in HRMECs, tube formation/migration assays

    PMID:40380281

    Open questions at the time
    • Whether PLTP activates AKT directly or through an intermediary receptor unknown
    • In vivo validation in diabetic retinopathy models not reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic-resolution structure of PLTP, the mechanism by which PLTP engages ABCA1 to trigger STAT3 signaling independently of lipid transfer, and the basis for context-dependent NF-κB activation versus suppression remain unresolved.
  • No high-resolution crystal or cryo-EM structure of human PLTP
  • ABCA1–PLTP signaling interface uncharacterized
  • Context determinants for pro- vs. anti-inflammatory NF-κB outcomes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 3 GO:0016787 hydrolase activity 1
Localization
GO:0005576 extracellular region 5 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 8 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
ABCA1APOA1APOEAURKARELA

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Recombinant human and mouse PLTP expressed in BHK cells possesses both phospholipid transfer activity and HDL conversion activity, demonstrating these are intrinsic functions of the PLTP protein. PLTP converts distinct HDL subspecies (Lp(A-I) and Lp(A-I/A-II)) into populations of larger and smaller particles. Eukaryotic cell expression of recombinant PLTP, functional assays for phospholipid transfer and HDL conversion Biochimica et biophysica acta High 7654777
1998 PLTP binds to both apoA-I and apoA-II, and the PLTP-binding domain on apoA-I resides in the amino-terminal region (residues 27–141), as demonstrated by solid-phase ligand binding assay, ELISA, apolipoprotein affinity chromatography, and monoclonal antibody epitope mapping. Solid-phase ligand binding assay, ELISA, affinity chromatography, monoclonal antibody inhibition studies Journal of lipid research High 9469594
1999 Molecular modeling of PLTP based on BPI crystal structure predicts a two-domain architecture with conserved N-terminal and C-terminal lipid-binding pockets. Site-directed mutagenesis of residues in these pockets abolishes phospholipid transfer activity. The N-terminal pocket mutants show reduced activity without altered HDL binding, while C-terminal pocket may mediate HDL association. A disulfide bridge between Cys146 and Cys185 is structurally essential. Homology modeling, site-directed mutagenesis, transient expression in HeLa cells, solid-phase HDL-binding assay Journal of lipid research High 10357844
1999 PLTP has an inherent serine esterase-type protease activity that cleaves apoA-I in the C-terminal portion between residues Ala196 and Thr197, generating a 23 kDa N-terminal fragment. The cleavage is inhibited by APMSF and chymostatin, and is reproduced by recombinant PLTP from CHO cells and baculovirus-insect cell systems. SDS-PAGE, Western blot, mass spectrometry, N-terminal sequencing, protease inhibitor studies, recombinant PLTP Journal of lipid research High 10191289
2000 Phospholipid transfer by PLTP is a prerequisite for PLTP-mediated HDL conversion. Chemical modification (DEPC or EMTS) of PLTP reduces both phospholipid transfer and HDL conversion activities in parallel. Recombinant N-terminal pocket mutants defective in phospholipid transfer cannot release apoA-I from HDL3 or generate prebeta-HDL. Chemical modification of PLTP, recombinant mutant proteins, native gradient gel electrophoresis, ultracentrifugation, crossed immunoelectrophoresis Biochemistry High 11123937
2002 Human plasma PLTP exists as two distinct forms: a high-activity form (HA-PLTP, ~160 kDa) associated with apoE and a low-activity form (LA-PLTP, ~520 kDa) complexed with apoA-I. The two forms differ in heparin-binding affinity and can be separated chromatographically. Heparin-Sepharose chromatography, gel filtration, SDS-PAGE, Western blot, immunoprecipitation, anti-apoE and anti-apoA-I immunoaffinity chromatography The Journal of biological chemistry High 11854286
2002 PLTP is a direct transcriptional target of LXR (liver X receptor): two functional LXR response elements (LXREs) were identified in the proximal promoter of the human PLTP gene, one a canonical DR4 and one a novel inverted repeat separated by 1 bp that also serves as an FXR response element. Affymetrix microarray, Northern blot, promoter LXRE characterization and reporter assay Journal of lipid research High 12454263
2003 HepG2-secreted PLTP co-elutes with apoE on gel filtration (~160 kDa), co-purifies with apoE on anti-apoE immunoaffinity chromatography, and anti-apoE antibodies inhibit PLTP activity, establishing a physical and functional interaction between PLTP and apoE in hepatic cells. Heparin-Sepharose affinity chromatography, size-exclusion chromatography, anti-apoE immunoaffinity chromatography, antibody inhibition of PLTP activity Journal of lipid research High 12810820
2003 Mast cell chymase degrades PLTP into specific fragments (70, 52, 48, 31 kDa), reducing both PLTP-mediated phospholipid transfer activity and pre-beta-HDL generation. Chymase also degrades PLTP-generated pre-beta-HDL particles, impairing high-affinity cholesterol efflux from macrophage foam cells. Immunoblot, phospholipid transfer assay, native gel electrophoresis, cholesterol efflux assay from foam cells The Journal of biological chemistry High 12531890
2004 PLTP functions as a transfer factor for alpha-tocopherol (vitamin E) in the brain. PLTP-deficient mice show significant brain alpha-tocopherol depletion, elevated oxidative stress markers (lipofuscin, cholesterol oxides, cellular peroxides), and increased anxiety behavior, establishing PLTP's role in brain vitamin E transport. PLTP knockout mouse model, alpha-tocopherol quantification, lipofuscin and cholesterol oxide measurement, elevated plus-maze behavioral testing FASEB journal High 15576481
2005 Exogenous recombinant PLTP added to primary human astrocytes significantly increases apoE secretion into conditioned medium, demonstrating that PLTP can regulate apoE secretion in brain cells. Recombinant PLTP treatment of primary human astrocyte cultures, PLTP activity assay, anti-apoE immunoaffinity chromatography, Western blot Journal of neuroscience research Medium 15795933
2008 Phospholipid transfer activity of PLTP is essential for atherogenesis: mice expressing a mutant PLTP that associates with HDL but lacks transfer activity show no change in HDL lipids, no stimulation of hepatic VLDL-TG secretion, and no increase in atherosclerotic lesion size, unlike mice expressing wild-type PLTP. Transgenic mice expressing transfer-inactive PLTP mutant, plasma lipid measurements, VLDL secretion assay, atherosclerosis quantification Journal of lipid research High 18711210
2008 Elevation of systemic PLTP (transgenic overexpression) impairs macrophage reverse cholesterol transport (RCT) in vivo, reducing plasma and fecal 3H-cholesterol tracer levels. Elevation of macrophage-specific PLTP alone does not affect RCT, indicating the systemic PLTP pool drives the impairment. In vivo RCT assay with 3H-cholesterol-loaded macrophages, PLTP transgenic and macrophage transplantation models, radioactivity quantification in plasma/liver/feces Atherosclerosis High 19100548
2008 Acute elevation of plasma PLTP activity in LDLR-knockout mice inhibits VLDL catabolism (at least partly by decreasing lipoprotein lipase activity), increases plasma VLDL-triglyceride levels, decreases HDL, and accelerates progression and destabilization of pre-existing atherosclerotic lesions. Conditional Tet-On transgenic mouse model, VLDL secretion assay, lipoprotein lipase activity measurement, atherosclerosis quantification, lesion composition analysis Arteriosclerosis, thrombosis, and vascular biology High 18421000
2009 PLTP localizes to the nucleus of neuroblastoma cells, cortical neurons, and transfected CHO/BHK cells. Nuclear export of PLTP is CRM1-dependent (blocked by leptomycin B). Secreted extracellular PLTP can enter cells and translocate to the nucleus, where it remains phospholipid transfer-active. Subcellular fractionation, leptomycin B inhibition, live-cell imaging, phospholipid transfer activity assay of nuclear fractions Biochimica et biophysica acta Medium 19321130
2011 PLTP (wild-type and lipid-transfer-inactive mutant PLTPM159E) increases nuclear levels of active pSTAT3(Tyr705) in macrophages via an ABCA1-dependent mechanism, and reduces nuclear NFκB p65 levels and pro-inflammatory cytokine secretion, demonstrating lipid-transfer-independent anti-inflammatory signaling. Recombinant wild-type and mutant PLTP treatment of differentiated THP1 cells and primary macrophages, nuclear fractionation, ABCA1 chemical inhibition and siRNA knockdown, ELISA for cytokines Biochimica et biophysica acta High 21782857
2012 Liver-specific PLTP expression in PLTP-null mice dramatically increases plasma non-HDL cholesterol, phospholipids, triglycerides, and apoB levels by enhancing VLDL lipidation in the hepatocyte microsomal lumen and increasing VLDL secretion, without affecting HDL lipids. Adenovirus-mediated liver-specific PLTP expression in PLTP-null mice, VLDL lipidation assay in hepatocyte microsomes, plasma VLDL secretion assay Hepatology High 22367708
2014 Cathepsin G (a serine protease) cleaves and inactivates PLTP in COPD bronchoalveolar lavage fluid. PLTP silencing (siRNA) in mice prior to LPS challenge increases ERK and NF-κB activation and pro-inflammatory cytokine levels; conversely, recombinant PLTP administration counters these effects, establishing an anti-inflammatory role for lung PLTP. BALF proteolytic activity assay, PLTP siRNA in mouse lungs, recombinant PLTP administration, ERK/NF-κB western blot, cytokine measurement, LPS lung injury model FASEB journal High 24532668
2014 PLTP deficiency increases BBB permeability in mice, decreases tight junction proteins (occludin, ZO-1, claudin-5), and elevates cerebrovascular ROS and lipid peroxidation. Dietary vitamin E supplementation in PLTP-KO mice restores BBB integrity and tight junction protein expression by reducing oxidative stress, linking PLTP's vitamin E transfer activity to BBB maintenance. In vivo multiphoton imaging, Evans blue assay, western blot for tight junction proteins, ROS and lipid peroxidation measurements, vitamin E dietary supplementation rescue Biochemical and biophysical research communications Medium 24513285
2015 PLTP deficiency in APP/PS1ΔE9 Alzheimer's model mice increases β-secretase activity and expression of γ-secretase catalytic units, shifts APP processing toward the amyloidogenic pathway, increases soluble Aβ peptides, and accelerates memory dysfunction, placing PLTP as a regulator of APP processing. PLTP/APP/PS1 double-knockout mouse model, β- and γ-secretase activity assays, Aβ ELISA, western blot, Morris water maze Human molecular genetics Medium 26160914
2015 PLTP deficiency in mice shifts CD4+ Th0 cell polarization toward the anti-inflammatory Th2 phenotype and significantly decreases production of the pro-Th1 cytokine IL-18 by accessory cells, establishing PLTP as a regulator of adaptive immune T-helper cell polarization. PLTP-KO mouse model, contact hypersensitivity model (DNFB), flow cytometry for T-cell subsets, cytokine measurements Cellular & molecular immunology Medium 26320740
2018 Electron microscopy reveals PLTP has a banana-shaped structure similar to CETP. PLTP penetrates into both HDL and LDL surfaces and forms a ternary PLTP-HDL-LDL complex, providing structural basis for the phospholipid transfer mechanism between lipoproteins. Electron microscopy (multiple EM techniques), single-particle analysis, lipoprotein interaction studies Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 29883800
2018 Both lipid-transfer-active and -inactive forms of recombinant PLTP directly stimulate pro-inflammatory cytokine production (IL-8, IL-6, VEGF, MMP3) and proliferation of rheumatoid arthritis fibroblast-like synoviocytes (FLS) via ABCA1 and STAT3 pathway activation, independently of lipid transfer activity. Recombinant active and inactive PLTP treatment of RA-FLS, ELISA for cytokines, 3H-thymidine proliferation assay, flow cytometry for ABCA1, STAT3 activation PloS one Medium 29565987
2019 PLTP deficiency protects mice from high-fat-diet-induced obesity and insulin resistance by enhancing insulin receptor and Akt phosphorylation in liver, adipose, and muscle, increasing GLUT4 in plasma membranes of adipocytes and muscle cells after insulin stimulation, and reducing sphingomyelins and free cholesterol in lipid rafts of hepatocyte plasma membranes. PLTP-KO mice on high-fat diet, western blot for insulin receptor/Akt phosphorylation, GLUT4 plasma membrane fractionation, lipid raft lipid composition analysis Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 31220615
2020 PLTP is identified as a batokine secreted by brown adipose tissue (BAT). Systemic or BAT-specific PLTP overexpression improves glucose tolerance, insulin sensitivity, and energy expenditure, and decreases plasma cholesterol/phospholipids/sphingolipids. The mechanism involves increased circulating bile acids that in turn enhance glucose uptake and thermogenesis in BAT, establishing PLTP as a mediator of BAT-liver interorgan communication. Proteomics/transcriptomics of human thermogenic adipocytes, BAT-specific and systemic PLTP overexpression mouse models, bile acid measurement, glucose tolerance and insulin sensitivity tests EMBO reports Medium 32672883
2022 PLTP is a direct transcriptional target of p53; its transactivation is impaired by cancer-associated p53 hypomorphs (P47S, Y107H, G334R). Enforced PLTP expression suppresses colony formation in human tumor cell lines and regulates cellular sensitivity to ferroptosis. RNA-seq in lymphoblastoid cell lines, p53 hypomorph comparison, PLTP overexpression colony formation assay, ferroptosis sensitivity assay The Journal of biological chemistry Medium 36309086
2012 CSE-induced TGF-β1 production and Smad3 phosphorylation in human alveolar epithelial cells is mediated through a Ras/ERK/PLTP pathway: ERK inhibition suppresses PLTP expression and TGF-β1 production; PLTP siRNA suppresses TGF-β1 and Smad3 activation downstream of ERK, without affecting Ras/ERK itself. ERK inhibitors, PLTP siRNA, Smad3 phosphorylation western blot, TGF-β1 ELISA in A549 cells Journal of cellular physiology Medium 22034170
2021 In vivo tracer studies using Orbitrap Lumos mass spectrometry show that PLTP is secreted in medium and large HDL (alpha2, alpha1, alpha0) and is transferred from medium to larger HDL sizes during circulation, from where it is catabolized. In vivo stable isotope tracer kinetics, targeted mass spectrometry (Orbitrap Lumos), compartmental modeling JCI insight Medium 33351780
2025 In diabetic retinopathy, PLTP promoter DNA hypermethylation mediated by DNMT3B suppresses PLTP expression in retinal endothelial cells. PLTP overexpression reverses high-glucose-induced impairment of endothelial migration and tube formation by promoting AKT and GSK3β phosphorylation, identifying PLTP as a regulator of retinal vascular function via the AKT/GSK3β pathway. siRNA for DNMT3B, luciferase reporter assay, PLTP overexpression in HRMECs, tube formation/migration assays, coimmunoprecipitation, GSK3β inhibitor, transcriptome sequencing Clinical epigenetics Medium 40380281
2025 PLTP promotes M2 macrophage polarization in hepatocellular carcinoma by binding to AURKA and p65, forming a ternary complex that induces p65 phosphorylation, activating NF-κB and upregulating IL-6, IL-8, and CSF-1. The PLTP functional domain (residues 25–245) mediates these interactions. Molecular docking, proteomics, coimmunoprecipitation, biochemical assays, PLTP overexpression in HCC, in vivo mouse models Advanced science Medium 41391040
2010 ApoA-I (and apolipoproteins E, A-II, A-IV) enhances PLTP phospholipid transfer activity in a concentration-dependent manner without affecting PLTP secretion or mass from macrophage foam cells, and protects PLTP from heat inactivation. THP-1 macrophage foam cell model, PLTP activity assay, PLTP mass ELISA, recombinant apolipoprotein addition Lipids in health and disease Medium 20534134

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The impact of phospholipid transfer protein (PLTP) on HDL metabolism. Atherosclerosis 188 11254896
1995 Functional expression of human and mouse plasma phospholipid transfer protein: effect of recombinant and plasma PLTP on HDL subspecies. Biochimica et biophysica acta 120 7654777
2002 Identification of PLTP as an LXR target gene and apoE as an FXR target gene reveals overlapping targets for the two nuclear receptors. Journal of lipid research 108 12454263
2004 Phospholipid transfer protein (PLTP) deficiency reduces brain vitamin E content and increases anxiety in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 93 15576481
2002 Isolation and partial characterization of the inactive and active forms of human plasma phospholipid transfer protein (PLTP). The Journal of biological chemistry 69 11854286
2011 Plasma PLTP (phospholipid-transfer protein): an emerging role in 'reverse lipopolysaccharide transport' and innate immunity. Biochemical Society transactions 61 21787334
2000 Quantification of human plasma phospholipid transfer protein (PLTP): relationship between PLTP mass and phospholipid transfer activity. Atherosclerosis 61 10924722
2004 PLTP deficiency improves the anti-inflammatory properties of HDL and reduces the ability of LDL to induce monocyte chemotactic activity. Journal of lipid research 58 15258196
1997 Similar organization of the lipopolysaccharide-binding protein (LBP) and phospholipid transfer protein (PLTP) genes suggests a common gene family of lipid-binding proteins. Genomics 58 9441745
2009 Plasma phospholipid transfer protein (PLTP): review of an emerging cardiometabolic risk factor. Obesity reviews : an official journal of the International Association for the Study of Obesity 56 19413703
2003 Widespread distribution of PLTP in human CNS: evidence for PLTP synthesis by glia and neurons, and increased levels in Alzheimer's disease. Journal of lipid research 56 12671035
2003 PLTP secreted by HepG2 cells resembles the high-activity PLTP form in human plasma. Journal of lipid research 53 12810820
2005 Anti-inflammatory effects of phospholipid transfer protein (PLTP) deficiency in mice. Biochimica et biophysica acta 49 15863365
1999 Structure and phospholipid transfer activity of human PLTP: analysis by molecular modeling and site-directed mutagenesis. Journal of lipid research 49 10357844
2006 Statins of different brain penetrability differentially affect CSF PLTP activity. Dementia and geriatric cognitive disorders 48 16960448
2000 PLTP activity in premenopausal women. Relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance. Journal of lipid research 48 10681407
1998 Binding of phospholipid transfer protein (PLTP) to apolipoproteins A-I and A-II: location of a PLTP binding domain in the amino terminal region of apoA-I. Journal of lipid research 47 9469594
2020 The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT-liver communication. EMBO reports 46 32672883
2011 PLTP regulates STAT3 and NFκB in differentiated THP1 cells and human monocyte-derived macrophages. Biochimica et biophysica acta 44 21782857
2005 Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro. Journal of neuroscience research 43 15795933
2012 The impact of phospholipid transfer protein (PLTP) on lipoprotein metabolism. Nutrition & metabolism 42 22897926
2007 Low phospholipid transfer protein (PLTP) is a risk factor for peripheral atherosclerosis. Atherosclerosis 42 17553507
2012 Liver phospholipid transfer protein (PLTP) expression with a PLTP-null background promotes very low-density lipoprotein production in mice. Hepatology (Baltimore, Md.) 41 22367708
2000 Phospholipid transfer is a prerequisite for PLTP-mediated HDL conversion. Biochemistry 41 11123937
2003 Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on LCAT, PLTP, and CETP in plasma and peripheral lymph in humans. Arteriosclerosis, thrombosis, and vascular biology 40 12893687
2012 Increased amyloid-β peptide-induced memory deficits in phospholipid transfer protein (PLTP) gene knockout mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 36 23303044
2008 Elevation of systemic PLTP, but not macrophage-PLTP, impairs macrophage reverse cholesterol transport in transgenic mice. Atherosclerosis 35 19100548
2001 The role of plasma phospholipid transfer protein (PLTP) in HDL remodeling in acute-phase patients. Biochimica et biophysica acta 35 11566452
2014 Phospholipid transfer protein (PLTP) deficiency impaired blood-brain barrier integrity by increasing cerebrovascular oxidative stress. Biochemical and biophysical research communications 34 24513285
2014 Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 24532668
2003 Decreased PLTP mass but elevated PLTP activity linked to insulin resistance in HTG: effects of bezafibrate therapy. Journal of lipid research 32 12754275
2017 Recombinant human plasma phospholipid transfer protein (PLTP) to prevent bacterial growth and to treat sepsis. Scientific reports 31 28596518
2001 Acute-phase HDL in phospholipid transfer protein (PLTP)-mediated HDL conversion. Atherosclerosis 31 11254899
2022 PLTP is a p53 target gene with roles in cancer growth suppression and ferroptosis. The Journal of biological chemistry 30 36309086
2021 New therapeutic horizons for plasma phospholipid transfer protein (PLTP): Targeting endotoxemia, infection and sepsis. Pharmacology & therapeutics 30 34974028
2018 Plasma lipid transfer proteins: The role of PLTP and CETP in atherogenesis. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 29 29558025
2003 PLTP activity decreases with weight loss: changes in PLTP are associated with changes in subcutaneous fat and FFA but not IAF or insulin sensitivity. Journal of lipid research 29 12837855
2001 Dynamic changes in mouse lipoproteins induced by transiently expressed human phospholipid transfer protein (PLTP): importance of PLTP in prebeta-HDL generation. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 29 11290460
1999 Phospholipid transfer protein (PLTP) causes proteolytic cleavage of apolipoprotein A-I. Journal of lipid research 29 10191289
1999 Serum phospholipid transfer protein activity and genetic variation of the PLTP gene. Atherosclerosis 26 10487493
2008 Acute elevation of plasma PLTP activity strongly increases pre-existing atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 25 18421000
2005 Genetic variation of PLTP modulates lipoprotein profiles in hypoalphalipoproteinemia. Journal of lipid research 25 16388083
2003 Degradation of phospholipid transfer protein (PLTP) and PLTP-generated pre-beta-high density lipoprotein by mast cell chymase impairs high affinity efflux of cholesterol from macrophage foam cells. The Journal of biological chemistry 24 12531890
2015 Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer's disease. Human molecular genetics 23 26160914
2002 Differences in reactivity of antibodies to active versus inactive PLTP significantly impacts PLTP measurement. Journal of lipid research 23 11861670
2015 Elevated baseline plasma phospholipid protein (PLTP) levels are an independent predictor of long-term all-cause mortality in patients with diabetes mellitus and known or suspected coronary artery disease. Atherosclerosis 22 25710294
2009 Relation of baseline plasma phospholipid transfer protein (PLTP) activity to left ventricular systolic dysfunction in patients referred for coronary angiography. Atherosclerosis 22 19446293
2007 Macrophage PLTP is atheroprotective in LDLr-deficient mice with systemic PLTP deficiency. Journal of lipid research 22 17928634
2002 Distribution of human plasma PLTP mass and activity in hypo- and hyperalphalipoproteinemia. Journal of lipid research 22 12177167
2018 PhosphoLipid transfer protein (PLTP) exerts a direct pro-inflammatory effect on rheumatoid arthritis (RA) fibroblasts-like-synoviocytes (FLS) independently of its lipid transfer activity. PloS one 21 29565987
2015 Cigarette smoke extract induces apoptosis of rat alveolar Type II cells via the PLTP/TGF-β1/Smad2 pathway. International immunopharmacology 21 26258626
2012 Ox-LDL-induced TGF-β1 production in human alveolar epithelial cells: involvement of the Ras/ERK/PLTP pathway. Journal of cellular physiology 21 22034170
2007 Atherogenic, enlarged, and dysfunctional HDL in human PLTP/apoA-I double transgenic mice. Journal of lipid research 21 17761633
2018 Structural basis of the lipid transfer mechanism of phospholipid transfer protein (PLTP). Biochimica et biophysica acta. Molecular and cell biology of lipids 20 29883800
1998 Oxidative modification of HDL3 in vitro and its effect on PLTP-mediated phospholipid transfer. Biochimica et biophysica acta 20 9555005
2009 Plasma PLTP activity is inversely associated with HDL-C levels. Nutrition & metabolism 19 19948027
2015 Plasma phospholipid transfer protein (PLTP) modulates adaptive immune functions through alternation of T helper cell polarization. Cellular & molecular immunology 18 26320740
2004 Effects of weight loss on PLTP activity and HDL particle size. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 18 15365582
2005 Phospholipid transfer protein (PLTP) mRNA expression is stimulated by developing embryos in the oviduct. Journal of cellular biochemistry 17 15832314
2021 Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos. JCI insight 16 33351780
2008 SAA and PLTP activity in plasma of periodontal patients before and after full-mouth tooth extraction. Oral diseases 16 18826383
2014 PLTP deficiency impairs learning and memory capabilities partially due to alteration of amyloid-β metabolism in old mice. Journal of Alzheimer's disease : JAD 15 24121956
2011 Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity. Journal of internal medicine 15 21973210
2019 Phospholipid transfer protein (PLTP) deficiency attenuates high fat diet induced obesity and insulin resistance. Biochimica et biophysica acta. Molecular and cell biology of lipids 14 31220615
2015 PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity. Journal of lipid research 14 26009633
2009 PLTP is present in the nucleus, and its nuclear export is CRM1-dependent. Biochimica et biophysica acta 14 19321130
2008 Plasma phospholipid transfer activity is essential for increased atherogenesis in PLTP transgenic mice: a mutation-inactivation study. Journal of lipid research 13 18711210
2001 Differential display reveals downregulation of the phospholipid transfer protein (PLTP) at the mRNA level in brains of patients with Down syndrome. Life sciences 13 11324722
1999 Introduction of the human PLTP transgene suppresses the atherogenic diet-induced increase in plasma phospholipid transfer activity in C57BL/6 mice. International journal of clinical & laboratory research 12 10356658
2022 Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS. International journal of molecular sciences 11 36362012
2018 Deletion of plasma Phospholipid Transfer Protein (PLTP) increases microglial phagocytosis and reduces cerebral amyloid-β deposition in the J20 mouse model of Alzheimer's disease. Oncotarget 11 29731975
2002 Role of hepatic lipase and scavenger receptor BI in clearing phospholipid/free cholesterol-rich lipoproteins in PLTP-deficient mice. Biochimica et biophysica acta 10 12117557
2013 High PLTP activity is associated with depressed left ventricular systolic function. Atherosclerosis 9 23545183
2010 Human apoA-I increases macrophage foam cell derived PLTP activity without affecting the PLTP mass. Lipids in health and disease 9 20534134
2012 Elevated expression of PLTP is atherogenic in apolipoprotein E deficient mice. Atherosclerosis 8 23313246
2011 Dry eye symptoms are increased in mice deficient in phospholipid transfer protein (PLTP). The American journal of pathology 8 21514421
2016 Overexpressed PLTP in macrophage may promote cholesterol accumulation by prolonged endoplasmic reticulum stress. Medical hypotheses 7 28012603
2011 Different phospholipid transfer protein complexes contribute to the variation in plasma PLTP specific activity. Biochimica et biophysica acta 7 21303701
2010 Synthesis of a series of novel 2,4,5-trisubstituted selenazole compounds as potential PLTP inhibitors. Bioorganic & medicinal chemistry letters 7 20667734
2010 Genetic association between PLTP gene polymorphisms and Alzheimer's disease in a Japanese population. Dementia and geriatric cognitive disorders 6 20714154
2007 Inducible expression of phospholipid transfer protein (PLTP) in transgenic mice: acute effects of PLTP on lipoprotein metabolism. Transgenic research 6 17437182
2016 Cigarette smoke extract induces the epithelial-to-mesenchymal transition via the PLTP/TGF-β1/Smad2 pathway in RLE-6TN cells. Toxicology research 4 30090492
2009 Reduction of HDL levels lowers plasma PLTP and affects its distribution among lipoproteins in mice. Biochimica et biophysica acta 4 19422933
2022 AGTR1, PLTP, and SCG2 associated with immune genes and immune cell infiltration in calcific aortic valve stenosis: analysis from integrated bioinformatics and machine learning. Mathematical biosciences and engineering : MBE 3 35341274
2025 DNA hypermethylation of PLTP mediated by DNMT3B aggravates vascular dysfunction in diabetic retinopathy via the AKT/GSK3β signaling pathway. Clinical epigenetics 2 40380281
2016 Serum CETP and PLTP activity in middle-aged men living in urban or rural area of the Lower Silesia region. PURE Poland sub-study. Archives of medical science : AMS 2 27478449
2011 [Study on the correlation between Chinese medical syndrome types and serum levels of PLTP and CETP in coronary heart disease patients]. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine 1 21823416
2025 Association of phospholipid transfer protein (PLTP) and the effect of genetic variant rs5072 on hypertriglyceridemia and atherogenic dyslipidemia in children and adolescents from Southeastern Mexico. Clinical biochemistry 0 39765303
2025 Fibrates Inhibit PLTP-induced M2 Macrophage Infiltration and Increase the Sensitivity of Hepatocellular Carcinoma to ICIs. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41391040
2021 Association between the PLTP rs4810479 SNP and Serum Lipid Traits in the Chinese Maonan and Han Populations. Genetics research 0 34385888