Affinage

PLTP

Phospholipid transfer protein · UniProt P55058

Length
493 aa
Mass
54.7 kDa
Annotated
2026-06-10
91 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLTP is a secreted lipid-transfer glycoprotein that remodels HDL and broadly governs plasma lipoprotein metabolism, transferring phospholipids between lipoproteins and converting HDL into larger and smaller subspecies while generating prebeta-HDL (PMID:7654777). Structurally it adopts a two-domain, banana-shaped architecture modeled on BPI and visualized by electron microscopy, with an N-terminal lipid-binding pocket that executes transfer and a C-terminal pocket that mediates HDL association; an intramolecular disulfide (Cys146-Cys185) is required for structural integrity, and PLTP penetrates both HDL and LDL surfaces to form a transient ternary PLTP-HDL-LDL complex (PMID:10357844, PMID:29883800). Phospholipid transfer is the obligate step driving HDL conversion and prebeta-HDL formation, as transfer-inactive mutants fail to release apoA-I or generate prebeta-HDL (PMID:11123937). In plasma PLTP circulates as a high-activity ~160 kDa form associated with apoE and a low-activity ~520 kDa form complexed with apoA-I, binding apoA-I through its amino-terminal residues 27-141 (PMID:9469594, PMID:11854286, PMID:12810820). The transfer activity is causally required for PLTP's metabolic effects in vivo: active PLTP stimulates hepatic VLDL lipidation and secretion and promotes atherosclerosis, whereas transfer-inactive PLTP does not (PMID:18711210, PMID:22367708). Beyond lipid transfer, PLTP delivers alpha-tocopherol (vitamin E) to the brain, where its loss depletes brain vitamin E and compromises blood-brain barrier integrity through oxidative stress (PMID:15576481, PMID:24513285). PLTP also exerts a lipid-transfer-independent, ABCA1-dependent anti-inflammatory program in macrophages, activating STAT3 and suppressing NF-kappaB (PMID:21782857). Its expression is transcriptionally controlled, being a direct LXR and p53 target gene (PMID:12454263, PMID:36309086), and its activity is post-translationally limited by proteolytic inactivation through cathepsin G and mast cell chymase (PMID:12531890, PMID:24532668). More recent work links PLTP to brown adipose tissue as a glucose-regulating batokine (PMID:32672883) and to tumor biology as a p53-responsive suppressor and modulator of macrophage polarization (PMID:36309086, PMID:41391040).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1995 High

    Establishing that a single recombinant protein carries both phospholipid transfer and HDL conversion activity defined PLTP as the enzyme responsible for HDL particle remodeling.

    Evidence Recombinant human/mouse PLTP expressed in BHK cells, in vitro HDL conversion assays

    PMID:7654777

    Open questions at the time
    • Did not establish whether the two activities are mechanistically coupled
    • No structural basis for activity
  2. 1998 High

    Mapping the apoA-I binding determinant to its N-terminal region (aa 27-141) identified the molecular contacts through which PLTP docks onto HDL apolipoproteins.

    Evidence Solid-phase ligand binding, ELISA with truncated apoA-I, antibody epitope mapping

    PMID:9469594

    Open questions at the time
    • Did not define the reciprocal PLTP surface engaging apoA-I
    • Functional consequence of binding not yet linked to transfer
  3. 1999 High

    A BPI-based structural model plus mutagenesis resolved the division of labor between the N-terminal transfer pocket and C-terminal HDL-binding pocket and identified an essential stabilizing disulfide.

    Evidence Molecular modeling on BPI X-ray structure, site-directed mutagenesis, transient HeLa expression with transfer and HDL-binding assays

    PMID:10357844

    Open questions at the time
    • Model not validated by direct PLTP structure determination
    • Catalytic mechanism of transfer unresolved
  4. 1999 High

    Detection of an intrinsic serine-esterase protease activity cleaving apoA-I raised the possibility that PLTP acts on lipoproteins beyond lipid transfer.

    Evidence SDS-PAGE, mass spectrometry, N-terminal sequencing, inhibitor profiling with plasma and recombinant PLTP

    PMID:10191289

    Open questions at the time
    • Physiological relevance of the protease activity not established
    • Not reconciled with lipid-transfer mechanism
  5. 2000 High

    Showing that abolishing phospholipid transfer abolishes HDL conversion established transfer as the obligatory upstream step for prebeta-HDL generation.

    Evidence Chemical modification and N-terminal pocket mutants, native gel electrophoresis, ultracentrifugation, crossed immunoelectrophoresis

    PMID:11123937

    Open questions at the time
    • Did not address transfer-independent functions later identified
    • In vitro only
  6. 2002 High

    Resolving plasma PLTP into apoE-associated high-activity and apoA-I-associated low-activity forms explained the heterogeneity of circulating PLTP activity.

    Evidence Multimodal chromatography, immunoprecipitation, gel filtration of human plasma

    PMID:11854286

    Open questions at the time
    • Mechanism converting HA-PLTP to LA-PLTP inferred, not directly demonstrated
    • Structural basis of activity difference unknown
  7. 2002 High

    Identification of functional LXR response elements in the PLTP promoter placed PLTP under sterol-sensing transcriptional control in macrophages.

    Evidence Microarray, Northern blot, luciferase reporter assays with LXRE mutagenesis in murine and human macrophages

    PMID:12454263

    Open questions at the time
    • In vivo relevance of LXR control to plasma PLTP not quantified
    • Other transcriptional inputs not addressed
  8. 2003 High

    Demonstrating apoE association of secreted PLTP and inhibition of activity by anti-apoE antibodies identified apoE as a functional partner of the high-activity form.

    Evidence HepG2 conditioned medium, anti-apoE immunoaffinity chromatography, antibody inhibition of activity

    PMID:12810820

    Open questions at the time
    • Stoichiometry and binding interface with apoE undefined
    • How apoE enhances activity unresolved
  9. 2003 High

    Mast cell chymase degradation of PLTP and prebeta-HDL revealed a proteolytic mechanism limiting PLTP-driven cholesterol efflux.

    Evidence In vitro chymase cleavage, immunoblot fragment mapping, transfer activity and macrophage foam cell cholesterol efflux assays

    PMID:12531890

    Open questions at the time
    • In vivo contribution of chymase to PLTP turnover not established
    • Cleavage sites not mapped
  10. 2004 High

    PLTP knockout mice with depleted brain vitamin E and oxidative damage extended PLTP function to alpha-tocopherol delivery in the CNS.

    Evidence PLTP KO mice, alpha-tocopherol and lipid peroxide quantification, behavioral testing

    PMID:15576481

    Open questions at the time
    • Molecular mechanism of tocopherol transfer not dissected
    • Tissue route of delivery not defined
  11. 2005 Medium

    Demonstrating PLTP secretion by CNS cells and its stimulation of astrocyte apoE secretion linked PLTP to brain lipoprotein metabolism.

    Evidence Western blot, activity assays in conditioned medium, immunohistochemistry, exogenous PLTP addition with apoE ELISA

    PMID:15795933

    Open questions at the time
    • Single readout in one lab
    • Mechanism by which PLTP increases apoE secretion unknown
  12. 2008 High

    Transgenic expression of transfer-inactive PLTP showed lipid transfer is necessary for PLTP's effects on HDL, VLDL secretion, and atherosclerosis in vivo.

    Evidence Transgenic mice expressing transfer-inactive PLTP, atherosclerosis diet model, plasma lipid and hepatic VLDL assays

    PMID:18711210

    Open questions at the time
    • Did not address transfer-independent signaling functions
    • Mechanism of VLDL stimulation not yet localized to hepatocyte
  13. 2008 High

    Acute PLTP elevation worsening lipoprotein profiles via reduced lipoprotein lipase activity identified a downstream metabolic mechanism for PLTP's atherogenicity.

    Evidence Inducible PLTP transgenic LDLR-KO mice, VLDL secretion, lipoprotein lipase activity, lesion analysis

    PMID:18421000

    Open questions at the time
    • How PLTP reduces LPL activity unresolved
    • Reversibility not tested
  14. 2009 Medium

    Discovery of CRM1-dependent nuclear export and active intranuclear PLTP raised the prospect of a non-secretory intracellular role.

    Evidence Subcellular fractionation, leptomycin B, live imaging, activity assay of nuclear fractions

    PMID:19321130

    Open questions at the time
    • Nuclear substrates or functions not identified
    • Single lab
  15. 2011 High

    Using a lipid-transfer-inactive mutant and ABCA1 loss-of-function established a transfer-independent anti-inflammatory STAT3/NF-kappaB signaling function in macrophages.

    Evidence Nuclear fractionation/Western blot, ABCA1 siRNA and glyburide, inactive PLTP mutant in THP1 and primary macrophages

    PMID:21782857

    Open questions at the time
    • Direct PLTP-ABCA1 interaction not demonstrated
    • Receptor-level mechanism of STAT3 activation unknown
  16. 2012 High

    Liver-specific PLTP expression localized the VLDL-stimulating activity to hepatocyte microsomal lipidation, defining PLTP's role in VLDL assembly.

    Evidence Adenoviral liver-specific PLTP in PLTP-null mice, microsomal lipidation and VLDL secretion assays

    PMID:22367708

    Open questions at the time
    • Intracellular site of PLTP action within the secretory pathway not pinpointed
    • Relationship to circulating PLTP unclear
  17. 2012 Medium

    Demonstrating apolipoprotein-specific enhancement of PLTP activity clarified how HDL apolipoproteins modulate and stabilize secreted PLTP.

    Evidence THP-1 foam cell conditioned medium, activity assays and heat-inactivation protection with purified apolipoproteins

    PMID:20534134

    Open questions at the time
    • Structural basis of activity enhancement not defined
    • Single lab
  18. 2014 Medium

    Linking PLTP loss to BBB breakdown reversible by vitamin E placed PLTP's tocopherol transfer upstream of cerebrovascular integrity.

    Evidence PLTP KO mice, multiphoton imaging, Evans blue, tight junction Western blots, vitamin E rescue

    PMID:24513285

    Open questions at the time
    • Cellular target of oxidative stress not identified
    • Single lab
  19. 2014 High

    Identifying cathepsin G as a PLTP-inactivating protease in lung and showing PLTP restrains LPS-induced inflammation extended proteolytic regulation and anti-inflammatory roles to the airway.

    Evidence Proteolytic cleavage assays, BALF activity, lung PLTP siRNA and recombinant PLTP in LPS model with ERK/NF-kappaB readouts

    PMID:24532668

    Open questions at the time
    • Cleavage sites not mapped
    • Relationship to chymase-mediated cleavage not compared
  20. 2015 Medium

    PLTP deficiency accelerating amyloid pathology in an Alzheimer's model implicated PLTP in APP processing and neuronal homeostasis.

    Evidence PLTP KO x APP/PS1 mice, behavioral tests, Abeta ELISA, secretase activity assays

    PMID:26160914

    Open questions at the time
    • Mechanism connecting PLTP to secretase activity unknown
    • Single lab
  21. 2018 Medium

    Electron microscopy of PLTP and a reconstituted ternary complex provided the structural basis for inter-lipoprotein phospholipid transfer.

    Evidence Negative-stain and cryo-EM single-particle analysis, ternary PLTP-HDL-LDL complex reconstitution

    PMID:29883800

    Open questions at the time
    • No atomic-resolution structure or mutagenesis validation
    • Single lab
  22. 2018 Medium

    Showing transfer-independent pro-inflammatory STAT3/ABCA1 signaling in synoviocytes generalized PLTP's signaling function beyond macrophages and beyond a purely protective role.

    Evidence Active and inactive recombinant PLTP on fibroblast-like synoviocytes, cytokine ELISA, proliferation and STAT3 assays

    PMID:29565987

    Open questions at the time
    • Context-dependence of pro- vs anti-inflammatory STAT3 outcome unexplained
    • Single lab
  23. 2019 Medium

    PLTP deficiency improving insulin sensitivity via reduced membrane sphingomyelin/cholesterol linked PLTP to lipid raft composition and insulin signaling.

    Evidence PLTP KO mice on high-fat diet, glucose/insulin tests, p-IR/p-Akt and GLUT4 fractionation, lipid raft composition analysis

    PMID:31220615

    Open questions at the time
    • Direct PLTP action on membrane lipids not demonstrated in situ
    • Single lab
  24. 2020 Medium

    Identifying PLTP as a brown adipose batokine acting through circulating bile acids defined a new endocrine role in glucose homeostasis and thermogenesis.

    Evidence Human thermogenic adipocyte proteomics/transcriptomics, BAT-specific and systemic PLTP overexpression, glucose/bile acid/energy expenditure measurements

    PMID:32672883

    Open questions at the time
    • Mechanism by which PLTP raises bile acids unresolved
    • Single lab
  25. 2021 Medium

    Human in vivo tracer studies established that PLTP is secreted on medium/large HDL and follows a catabolic route distinct from CETP and LCAT.

    Evidence Stable-isotope tracer infusion, targeted mass spectrometry and compartmental modeling in 6 participants

    PMID:33351780

    Open questions at the time
    • Small sample size
    • Molecular determinants of HDL-size association not defined
  26. 2022 Medium

    Establishing PLTP as a p53 transcriptional target with tumor-suppressive and ferroptosis-modulating activity connected PLTP to the p53 stress-response network.

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

    PMID:36309086

    Open questions at the time
    • Mechanism linking PLTP to ferroptosis not defined
    • Single ferroptosis assay
  27. 2025 Medium

    Identifying a PLTP-AURKA-p65 complex driving NF-kappaB-dependent M2 macrophage polarization revealed a protein-protein-interaction mechanism in hepatocellular carcinoma.

    Evidence Co-IP, docking, proteomics, p-p65 Western blots, cytokine ELISA, GMB-475 inhibitor in orthotopic and Myc-driven HCC models

    PMID:41391040

    Open questions at the time
    • Reciprocal validation and binding interface incompletely defined
    • Single lab
  28. 2025 Medium

    Showing DNMT3B-mediated promoter hypermethylation silences PLTP and that PLTP drives AKT/GSK3beta signaling defined epigenetic control and a vascular signaling axis in diabetic retinopathy.

    Evidence DNMT3B siRNA, luciferase reporter, co-IP, transcriptomics, migration/tube formation assays in HRMECs, STZ mouse model

    PMID:40380281

    Open questions at the time
    • Direct PLTP receptor/effector for AKT activation unidentified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PLTP's lipid-transfer-independent signaling functions are physically transduced — including the receptor or membrane events linking PLTP to ABCA1/STAT3, the basis of intranuclear activity, and the determinants of its context-dependent pro- versus anti-inflammatory output — remains unresolved.
  • No defined receptor for PLTP signaling
  • Nuclear function and substrates undefined
  • Atomic-resolution structure with mutational validation lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0140104 molecular carrier activity 3 GO:0060089 molecular transducer activity 2 GO:0016787 hydrolase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005576 extracellular region 4 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ABCA1APOA1APOA2APOEAURKARELASTAT3
Complex memberships
PLTP-AURKA-p65 complexPLTP-HDL-LDL ternary complexhigh-activity PLTP-apoE complexlow-activity PLTP-apoA-I complex

Evidence

Reading pass · 28 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, converting two distinct HDL subspecies (Lp(A-I) and Lp(A-I/A-II)) into larger and smaller particles in vitro. Eukaryotic cell expression of cDNA (BHK cells), in vitro HDL conversion assay with purified plasma-derived and recombinant PLTP Biochimica et biophysica acta High 7654777
1998 PLTP binds to both apolipoprotein A-I and apoA-II; the PLTP-binding domain on apoA-I resides in the amino-terminal region (amino acids 27–141), as demonstrated by solid-phase ligand binding, ELISA displacement, and inhibition with anti-apoA-I monoclonal antibodies. Solid-phase ligand binding assay, ELISA with truncated recombinant apoA-I forms, apoA-I/apoA-II affinity chromatography, monoclonal antibody epitope mapping Journal of lipid research High 9469594
1999 Structure of PLTP was modeled on the BPI X-ray structure, predicting a two-domain architecture with conserved lipid-binding pockets. Site-directed mutagenesis of N-terminal pocket residues abolished phospholipid transfer activity without impairing HDL binding, while C-terminal pocket mutations affected HDL association. A disulfide bridge between Cys146 and Cys185 is essential for structural integrity. Molecular modeling based on BPI X-ray structure, site-directed mutagenesis, transient expression in HeLa cells, phospholipid transfer activity assay, solid-phase HDL-binding assay Journal of lipid research High 10357844
1999 PLTP has an inherent serine esterase-type protease activity: incubation with HDL3 or purified apoA-I causes proteolytic cleavage of apoA-I between residues Ala196 and Thr197 (generating a 23 kDa C-terminal fragment), inhibitable by APMSF and chymostatin. This activity was reproduced with recombinant PLTP from CHO and baculovirus systems. SDS-PAGE, Western blot, mass spectrometry, N-terminal sequencing, protease inhibitor experiments, in vitro incubation assay with purified plasma and recombinant PLTP Journal of lipid research High 10191289
2000 Phospholipid transfer is a prerequisite for PLTP-mediated HDL conversion: chemical modification of PLTP that reduces phospholipid transfer activity in parallel reduces HDL conversion; recombinant PLTP mutants defective in N-terminal lipid-binding pocket activity are unable to release apoA-I from HDL3 or generate prebeta-HDL particles. Chemical modification (DEPC, ethylmercurithiosalicylate), recombinant mutant protein production, native gradient gel electrophoresis, ultracentrifugation, crossed immunoelectrophoresis Biochemistry High 11123937
2002 Two forms of PLTP exist in human plasma: a high-activity form (HA-PLTP, ~160 kDa) associated with apoE but not apoA-I, and a low-activity form (LA-PLTP, ~520 kDa) complexed with apoA-I. LA-PLTP shows higher affinity for heparin-Sepharose than HA-PLTP; the model proposed is that nascent PLTP enters circulation as HA-PLTP and is transferred to apoA-I-containing HDL, becoming the LA-PLTP complex. Heparin-Sepharose chromatography, hydrophobic interaction chromatography, anti-PLTP immunoaffinity chromatography, hydroxylapatite chromatography, SDS-PAGE, Western blot, immunoprecipitation, gel filtration The Journal of biological chemistry High 11854286
2002 PLTP is a direct transcriptional target of liver X receptor (LXR): LXR ligands induce PLTP 6-fold in murine and human macrophages, and two functional LXR response elements (one classic DR4, one novel IR1 identical to FXR response element) were identified and characterized in the proximal PLTP promoter. Affymetrix microarray, Northern blot, luciferase reporter assay with LXR response element mutations Journal of lipid research High 12454263
2003 PLTP secreted by HepG2 hepatoma cells co-elutes with apolipoprotein E (apoE) by size-exclusion chromatography and is retained on anti-apoE immunoaffinity columns; anti-apoE antibodies inhibit PLTP activity, indicating a functional interaction between PLTP and apoE in the high-activity form. Heparin-Sepharose affinity chromatography, size-exclusion chromatography, anti-apoE immunoaffinity chromatography, PLTP activity assay, antibody inhibition Journal of lipid research High 12810820
2003 Mast cell chymase proteolytically degrades PLTP into fragments (70, 52, 48, and 31 kDa), reducing its phospholipid transfer activity and ability to generate prebeta-HDL. Chymase also degrades pre-beta-HDL particles generated by PLTP, significantly inhibiting the high-affinity component of cholesterol efflux from macrophage foam cells. Immunoblot, in vitro chymase cleavage assay, phospholipid transfer activity assay, cholesterol efflux assay from macrophage 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 (-30%), accompanied by elevated lipofuscin, cholesterol oxides, and cellular peroxides, and increased anxiety behavior. PLTP knockout mouse model, alpha-tocopherol quantification, lipid peroxide assays, elevated plus-maze behavioral test FASEB journal High 15576481
2005 PLTP is synthesized and secreted as an active protein by neurons, microglia, and astrocytes in culture; exogenous recombinant PLTP added to primary human astrocytes significantly increases apoE secretion into conditioned medium, linking PLTP activity to apoE metabolism in the CNS. Western blot, phospholipid transfer activity assay in cell-conditioned medium, PLTP immunohistochemistry, exogenous recombinant PLTP addition to astrocyte cultures, apoE ELISA Journal of neuroscience research Medium 15795933
2008 Phospholipid transfer activity of PLTP is essential for its atherogenic effects: mice expressing a transfer-inactive PLTP mutant (still able to associate with HDL) show no changes in HDL lipid levels, no stimulation of hepatic VLDL-TG secretion, and no increase in atherosclerotic lesion size, unlike mice expressing active PLTP. Transgenic mouse model expressing mutant PLTP (transfer-inactive), cholesterol-enriched diet atherosclerosis model, plasma lipid assays, hepatic VLDL secretion assay Journal of lipid research High 18711210
2008 Acute elevation of plasma PLTP activity in LDL receptor knockout mice inhibits VLDL catabolism (at least partly by decreasing lipoprotein lipase activity), increases plasma VLDL levels, decreases HDL, and accelerates progression and destabilization of pre-existing atherosclerotic lesions. Conditional tetracycline-inducible PLTP transgenic mouse model, plasma lipid assays, VLDL secretion assay, lipoprotein lipase activity assay, atherosclerosis lesion analysis Arteriosclerosis, thrombosis, and vascular biology High 18421000
2009 PLTP localizes to the nucleus of cells that constitutively express it and of PLTP-transfected cells; nuclear export of PLTP is CRM1-dependent (blocked by leptomycin B); secreted extracellular PLTP can re-enter cells and translocate to the nucleus; intranuclear PLTP retains phospholipid transfer activity. Subcellular fractionation, leptomycin B treatment, live-cell imaging, phospholipid transfer activity assay of nuclear fractions, transfection of CHO/BHK cells Biochimica et biophysica acta Medium 19321130
2011 PLTP activates the STAT3 anti-inflammatory pathway in macrophages via ABCA1: incubation with wild-type PLTP or a lipid-transfer-inactive PLTP mutant (M159E) both increase nuclear pSTAT3(Tyr705), and this effect is reversed by ABCA1 chemical inhibition (glyburide) or ABCA1 siRNA knockdown. PLTP also reduces nuclear NFκB p65 levels and pro-inflammatory cytokine secretion. Nuclear fractionation, Western blot for pSTAT3 and NFκB p65, ELISA for cytokines, ABCA1 inhibitor, ABCA1 siRNA, lipid-transfer-inactive PLTP mutant, differentiated THP1 cells and primary human macrophages Biochimica et biophysica acta High 21782857
2012 Liver-specific PLTP expression (in PLTP-null background) dramatically increases plasma VLDL levels (non-HDL cholesterol 2.7-fold, apoB 2.2-fold) by increasing VLDL lipidation in hepatocyte microsomal lumina and VLDL secretion, without significantly affecting HDL. Adenovirus-mediated liver-specific PLTP expression in PLTP-null mice, VLDL secretion assay, hepatocyte microsomal lipidation assay, plasma lipoprotein profiling Hepatology High 22367708
2014 PLTP deficiency impairs blood-brain barrier integrity by increasing cerebrovascular oxidative stress (elevated ROS, 4-HNE, reduced SOD activity), leading to decreased expression of tight junction proteins occludin, ZO-1, and claudin-5; dietary vitamin E supplementation rescues BBB integrity, placing PLTP's vitamin E transfer activity upstream of BBB maintenance. PLTP knockout mice, in vivo multiphoton imaging, Evans blue assay, Western blot for tight junction proteins, ROS/lipid peroxidation assays, vitamin E dietary rescue Biochemical and biophysical research communications Medium 24513285
2014 Cathepsin G (a serine protease) cleaves and inactivates PLTP in the lung: PLTP activity in COPD bronchoalveolar lavage is reduced 80% due to cathepsin G-mediated degradation. PLTP siRNA silencing in mouse lungs increases ERK/NF-κB activation and inflammatory cell infiltration after LPS challenge, while recombinant PLTP protein counters these effects. Proteolytic cleavage assay, PLTP activity assay in BALF, PLTP siRNA in mouse lung (LPS model), recombinant PLTP administration, Western blot for ERK/NF-κB, ELISA for cytokines FASEB journal High 24532668
2015 PLTP deficiency in an APP/PS1 Alzheimer's model accelerates memory dysfunction and increases Aβ peptides by enhancing the amyloidogenic APP processing pathway (increased β- and γ-secretase activity), and reduces BDNF levels; autophagic dysfunction is also observed in PLTP-deficient AD model mice. PLTP KO × APP/PS1ΔE9 double-mutant mice, Morris water maze, ELISA for Aβ40/42, Western blot for APP/secretase subunits, secretase activity assays Human molecular genetics Medium 26160914
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 a structural basis for its phospholipid transfer mechanism between lipoproteins. Negative-stain electron microscopy, cryo-EM, single-particle analysis, ternary complex reconstitution Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 29883800
2018 In rheumatoid arthritis fibroblast-like synoviocytes (FLS), both lipid-transfer-active and lipid-transfer-inactive recombinant PLTP increase pro-inflammatory cytokine production (IL-8, IL-6, VEGF, MMP3) and cell proliferation, and activate the STAT3 pathway via ABCA1; this pro-inflammatory effect is independent of PLTP's lipid transfer activity. Recombinant active and inactive PLTP treatment of FLS, ELISA for cytokines, [3H]-thymidine proliferation assay, ABCA1 flow cytometry, STAT3 Western blot 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; PLTP-deficient cells show increased GLUT4 at plasma membranes after insulin stimulation; mechanistically, PLTP deficiency reduces sphingomyelin and free cholesterol content in lipid rafts/plasma membranes, providing a molecular basis for improved insulin sensitivity. PLTP knockout mouse model, high-fat diet, glucose/insulin tolerance tests, Western blot for p-IR/p-Akt, plasma membrane GLUT4 fractionation, lipid raft lipid composition analysis Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 31220615
2020 PLTP is a batokine secreted by brown adipose tissue (BAT): proteomics/transcriptomics in human thermogenic adipocytes identified PLTP; BAT-specific or systemic PLTP overexpression improves glucose tolerance and insulin sensitivity, increases energy expenditure, and reduces circulating cholesterol/phospholipids/sphingolipids. These effects are mediated by increased circulating bile acids, which enhance glucose uptake and thermogenesis in BAT. Proteomics and transcriptomics in human thermogenic adipocytes, BAT-specific and systemic PLTP overexpression in mice, glucose/insulin tolerance tests, bile acid measurements, energy expenditure measurements EMBO reports Medium 32672883
2022 PLTP is a p53 transcriptional target gene: three cancer-associated hypomorphic p53 variants show impaired PLTP transactivation by RNA-seq; enforced PLTP expression suppresses colony formation in human tumor cell lines and regulates ferroptosis sensitivity. RNA-seq in lymphoblastoid cell lines with p53 hypomorphs, colony formation assay with PLTP overexpression, ferroptosis sensitivity assay The Journal of biological chemistry Medium 36309086
2025 PLTP promotes M2 macrophage polarization in hepatocellular carcinoma by binding to aurora kinase A (AURKA) and p65, forming a ternary complex that induces p65 phosphorylation and activates NF-κB, upregulating IL-6, IL-8, and CSF-1; the PLTP inhibitor GMB-475 (binding PLTP's 25–245 AA domain) competitively disrupts this complex and reduces M2 infiltration in vivo. Co-immunoprecipitation, molecular docking, proteomics, Western blot for p-p65/NF-κB targets, ELISA for cytokines, GMB-475 treatment in orthotopic and Myc-driven HCC mouse models Advanced science Medium 41391040
2025 In diabetic retinopathy, DNMT3B-mediated DNA hypermethylation of the PLTP promoter suppresses PLTP expression; PLTP overexpression reverses high-glucose-induced impairment of endothelial cell migration and tube formation, and promotes AKT and GSK3β phosphorylation, placing PLTP upstream of the AKT/GSK3β signaling pathway in retinal vascular function. siRNA knockdown of DNMT3B, luciferase reporter assay, co-immunoprecipitation, transcriptome sequencing, GSK3β inhibitor, tube formation and migration assays in HRMECs, streptozotocin mouse model Clinical epigenetics Medium 40380281
2012 ApoA-I (and also apoE, apoA-II, apoA-IV but not immunoglobulins or BSA) enhances the phospholipid transfer activity of PLTP secreted from macrophage foam cells without affecting PLTP mass or secretion; apoA-I also protects PLTP from heat inactivation. THP-1 monocyte-derived macrophage foam cell model, PLTP activity assay in conditioned medium, PLTP ELISA, incubation with purified apolipoproteins and plasma-derived PLTP Lipids in health and disease Medium 20534134
2021 In vivo tracer/mass spectrometry studies show PLTP is secreted associated with medium and large HDL (alpha2, alpha1, alpha0) and is transferred from medium to larger HDL sizes during circulation, from which it is catabolized; this metabolic behavior is distinct from CETP and LCAT. In vivo stable-isotope tracer infusion, targeted mass spectrometry (Orbitrap Lumos), compartmental modeling across multiple HDL sizes in 6 human participants JCI insight Medium 33351780

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The impact of phospholipid transfer protein (PLTP) on HDL metabolism. Atherosclerosis 190 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 109 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 57 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 50 15863365
2006 Statins of different brain penetrability differentially affect CSF PLTP activity. Dementia and geriatric cognitive disorders 49 16960448
1999 Structure and phospholipid transfer activity of human PLTP: analysis by molecular modeling and site-directed mutagenesis. Journal of lipid research 49 10357844
2020 The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT-liver communication. EMBO reports 48 32672883
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 48 9469594
2011 PLTP regulates STAT3 and NFκB in differentiated THP1 cells and human monocyte-derived macrophages. Biochimica et biophysica acta 47 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 Liver phospholipid transfer protein (PLTP) expression with a PLTP-null background promotes very low-density lipoprotein production in mice. Hepatology (Baltimore, Md.) 42 22367708
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
2000 Phospholipid transfer is a prerequisite for PLTP-mediated HDL conversion. Biochemistry 42 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 37 23303044
2014 Phospholipid transfer protein (PLTP) deficiency impaired blood-brain barrier integrity by increasing cerebrovascular oxidative stress. Biochemical and biophysical research communications 36 24513285
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 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 33 12754275
2022 PLTP is a p53 target gene with roles in cancer growth suppression and ferroptosis. The Journal of biological chemistry 32 36309086
2021 New therapeutic horizons for plasma phospholipid transfer protein (PLTP): Targeting endotoxemia, infection and sepsis. Pharmacology & therapeutics 32 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 31 29558025
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
1999 Phospholipid transfer protein (PLTP) causes proteolytic cleavage of apolipoprotein A-I. Journal of lipid research 30 10191289
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 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
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 24 26160914
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
2002 Differences in reactivity of antibodies to active versus inactive PLTP significantly impacts PLTP measurement. Journal of lipid research 23 11861670
2018 Structural basis of the lipid transfer mechanism of phospholipid transfer protein (PLTP). Biochimica et biophysica acta. Molecular and cell biology of lipids 22 29883800
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
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
2021 Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos. JCI insight 18 33351780
2015 Plasma phospholipid transfer protein (PLTP) modulates adaptive immune functions through alternation of T helper cell polarization. Cellular & molecular immunology 18 26320740
2005 Phospholipid transfer protein (PLTP) mRNA expression is stimulated by developing embryos in the oviduct. Journal of cellular biochemistry 18 15832314
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
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
2009 PLTP is present in the nucleus, and its nuclear export is CRM1-dependent. Biochimica et biophysica acta 15 19321130
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
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
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 12 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 12 29731975
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
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
2025 DNA hypermethylation of PLTP mediated by DNMT3B aggravates vascular dysfunction in diabetic retinopathy via the AKT/GSK3β signaling pathway. Clinical epigenetics 3 40380281
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
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 3 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
2026 Phospholipid Transfer Protein (PLTP) in Cholesterol Handling: Implications for Mitochondrial Lipid Homeostasis in Human iPSC-Derived Cardiomyocytes. International journal of molecular sciences 0 42074254
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

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