Affinage

FABP5

Fatty acid-binding protein 5 · UniProt Q01469

Length
135 aa
Mass
15.2 kDa
Annotated
2026-06-09
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FABP5 (epidermal fatty acid-binding protein) is an intracellular lipid chaperone that binds long-chain saturated and unsaturated fatty acids — including arachidonic, linoleic, and docosahexaenoic acids — within a β-barrel of ten anti-parallel β-strands, coupling cytosolic lipid metabolism to nuclear and signaling outputs (PMID:12049637, PMID:18513372, PMID:38777142). Its central regulatory feature is ligand-gated nuclear import: 'activating' cis-bonded polyunsaturated fatty acids permit allosteric communication between the β2 ligand-sensing loop and a tertiary nuclear localization signal in the α-helical cap, driving cytoplasm-to-nucleus translocation, whereas saturated fatty acids destabilize this activation loop (PMID:24692551). Once nuclear, FABP5 delivers fatty acid ligands to PPARβ/δ and PPARγ to potentiate their transcriptional activity, a function essential for HER2-driven mammary tumorigenesis and for shuttling arachidonic acid to PPARβ/δ in brain to support hippocampal learning (PMID:23722546, PMID:24644281, PMID:39357545). FABP5 simultaneously governs endocannabinoid disposition by carrying anandamide to FAAH for hydrolysis, modulating CB1 signaling in nociceptors and controlling GIP secretion in intestinal K cells (PMID:24644281, PMID:25268051, PMID:35655086). Beyond nuclear receptors, FABP5 directly binds Raptor to assemble functional mTORC1 in response to ω-6 linoleic acid, and engages additional partners — VCP to drive NF-κB-dependent neutrophil recruitment, HIF-1α to enhance its synthesis, FASN to direct its proteasomal degradation, and asprosin to enable nuclear inhibition of PPARα (PMID:40080571, PMID:37967009, PMID:33128030, PMID:37416772, PMID:40231957). In immune cells FABP5 programs long-chain unsaturated fatty acid metabolism, fatty acid β-oxidation, and macrophage M2/immunosuppressive polarization, and shapes T cell and Th17 responses (PMID:36384126, PMID:39357545, PMID:34400394, PMID:40074327); in keratinocytes it promotes differentiation through 13(S)-HODE-driven NF-κB signaling (PMID:21068754, PMID:23528210). Its activity is tuned post-translationally by S-glutathionylation at Cys127 and by ubiquitination of the NLS domain by TRIM45 (K33/K63) or stabilization via MELK (K48), all of which favor nuclear translocation and PPAR engagement (PMID:34876574, PMID:38755308, PMID:39871325).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 High

    Establishing the three-dimensional fold and dynamics of FABP5 was the prerequisite for understanding how it sequesters and releases lipid ligands.

    Evidence Multidimensional NMR structure determination with 15N relaxation and H/D exchange of human E-FABP

    PMID:12049637

    Open questions at the time
    • Did not define ligand-bound conformational changes
    • No link between dynamics and nuclear translocation yet
  2. 2008 Medium

    Defining FABP5's ligand spectrum and a cellular requirement showed it is a broad long-chain fatty acid carrier with functional consequences in neurons.

    Evidence Radiobinding analysis plus antisense knockdown and recombinant protein rescue in NGF-differentiated PC12 cells

    PMID:18513372

    Open questions at the time
    • Did not resolve molecular downstream effector for neurite outgrowth
    • Nuclear vs cytoplasmic roles not separated
  3. 2013 High

    Genetic epistasis established FABP5 as the lipid-delivery arm of PPARβ/δ transcriptional signaling driving proliferation.

    Evidence FABP5-null × MMTV-ErbB2 mouse cross plus ectopic expression with PPARδ target gene readouts

    PMID:23722546

    Open questions at the time
    • Identity of the operative endogenous ligand not pinned down
    • Mechanism of nuclear import not yet structural
  4. 2014 High

    A crystal structure resolved how specific polyunsaturated fatty acids allosterically expose the NLS, providing the atomic basis for ligand-selective nuclear translocation.

    Evidence X-ray crystallography, HDX-MS, fluorescence anisotropy and translocation assays comparing linoleic/arachidonic vs saturated fatty acids

    PMID:24692551

    Open questions at the time
    • Did not capture the nuclear receptor handoff structurally
    • Cellular ligand-sensing kinetics not measured
  5. 2014 High

    Knockout studies revealed a dual role in endocannabinoid biology — FABP5 both promotes anandamide hydrolysis and delivers arachidonic acid to nuclear PPARβ/δ — linking it to learning and hormone secretion.

    Evidence FABP5-KO mice with AEA quantification, PPARβ/δ target genes, behavioral testing, and GIP reporter knock-in mice

    PMID:24644281 PMID:25268051

    Open questions at the time
    • Relative flux to FAAH vs nucleus in vivo unquantified
    • Tissue-specific partitioning of the two functions unresolved
  6. 2010 High

    Defined a lipid-metabolite pathway whereby FABP5 channels linoleic acid to 13(S)-HODE to activate NF-κB and drive keratinocyte differentiation.

    Evidence E-FABP KO keratinocytes with linoleic acid incorporation, 13(S)-HODE quantification, NF-κB reporters and differentiation markers

    PMID:21068754 PMID:23528210

    Open questions at the time
    • Mechanism by which FABP5 enhances LA incorporation unresolved
    • Direct vs indirect role in NF-κB activation not separated
  7. 2021 High

    Identifying S-glutathionylation at Cys127 showed redox state directly gates FABP5 nuclear translocation and PPARβ/δ engagement, tying oxidative signaling to its activity.

    Evidence Redox proteomics, Cys127 mutagenesis, nuclear fractionation, FABP5-PPARβ/δ Co-IP, Grx1 conditional KO mice

    PMID:34876574

    Open questions at the time
    • Structural effect of Cys127 modification on NLS not solved
    • Crosstalk with ligand-induced translocation unclear
  8. 2022 High

    Conditional and tissue-specific knockouts established FABP5 as a programmer of immune cell lipid metabolism, controlling macrophage polarization and inflammatory tone through PPARγ, AMPK and NF-κB.

    Evidence Myeloid- and keratinocyte-specific KO mice with lipidomics, metabolic flux, AMPK/NF-κB analysis, and VCP partner identification in psoriasis models

    PMID:36384126 PMID:36426981 PMID:37967009

    Open questions at the time
    • Whether PPARγ, AMPK and VCP routes operate in parallel or sequentially unresolved
    • Direct ligand sensed in each immune context not defined
  9. 2024 Medium

    Discovery of NLS-domain ubiquitination by TRIM45 and K48 stabilization by MELK added a ubiquitin-code layer controlling FABP5 nuclear translocation and stability.

    Evidence IP-MS, linkage-specific ubiquitination assays (K33/K63 and K48R), nuclear fractionation, FABP5-PPARγ Co-IP and Akt/mTOR readouts

    PMID:38755308 PMID:39871325

    Open questions at the time
    • Interplay between ubiquitination and glutathionylation not tested
    • Deubiquitinases not identified
  10. 2025 High

    Direct binding to Raptor revealed a nuclear-receptor-independent function — FABP5 acts as a linoleic acid sensor that assembles functional mTORC1.

    Evidence Co-IP of FABP5-Raptor, in vitro binding, mTORC1 activity assays in FABP5-KO cells with linoleic acid

    PMID:40080571

    Open questions at the time
    • Structural basis of the FABP5-Raptor interface unknown
    • Whether ligand binding modulates Raptor engagement unresolved
  11. 2025 Medium

    FABP5 was shown to carry asprosin into the nucleus to inhibit PPARα, extending its chaperone role to a protein cargo with metabolic-disease consequences.

    Evidence Asprosin-FABP5 Co-IP, nuclear fractionation, PPRE ChIP/reporter assays, and hepatic GalNAc-siRNA in a MASLD model

    PMID:40231957

    Open questions at the time
    • Whether asprosin uses the lipid-gated NLS mechanism unknown
    • Single-lab finding without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple competing inputs — ligand identity, Cys127 redox state, TRIM45/MELK ubiquitination, and protein partners (Raptor, VCP, HIF-1α, FASN, asprosin) — are integrated to determine FABP5 localization and which output pathway is engaged in a given cell remains unresolved.
  • No unified model reconciling cytoplasmic Raptor binding vs nuclear PPAR delivery
  • Quantitative hierarchy of PTMs and partners untested
  • Structural basis for most protein-protein interactions absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0140104 molecular carrier activity 4 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2
Partners
FASNHIF1APPARDPPARGRPTORS100A7TRIM45VCP
Complex memberships
mTORC1

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Crystal structure and biochemical analysis revealed that 'activating' polyunsaturated fatty acids (linoleic and arachidonic acid) induce FABP5 cytoplasmic-to-nuclear translocation by permitting allosteric communication between the ligand-sensing β2 loop and a tertiary nuclear localization signal within the α-helical cap. More saturated, non-activating fatty acids inhibit NLS formation by destabilizing the activation loop, implicating FABP5 specifically in cis-bonded polyunsaturated fatty acid signaling to PPARβ/δ. X-ray crystallography, HDX-MS, fluorescence anisotropy, nuclear translocation assays with linoleic acid vs. saturated fatty acids The Journal of biological chemistry High 24692551
2002 NMR solution structure of human E-FABP determined, consisting of 10 anti-parallel β-strands forming a β-barrel. Backbone dynamics showed uniformly low mobility (average order parameter S²=0.88), distinct from heart-type FABP, with hydrogen-bond network stability correlating with conformational exchange on the millisecond-to-microsecond timescale. Multi-dimensional NMR spectroscopy, ¹⁵N relaxation experiments (T1, T2, heteronuclear NOE), hydrogen/deuterium exchange The Biochemical journal High 12049637
2013 FABP5 shuttles fatty acid ligands from the cytosol to the nuclear receptor PPARβ/δ, enhancing its transcriptional activity. Genetic ablation of FABP5 in MMTV-ErbB2/HER2 oncomice relieved activation of EGFR downstream effector signals, decreased expression of PPARδ target genes driving cell proliferation, and suppressed mammary tumor development, establishing FABP5 as essential for HER2-driven mammary tumorigenesis. Genetic knockout (FABP5-null × MMTV-ErbB2 mice), ectopic expression in 3T3 fibroblasts, PPARδ target gene expression, downstream signaling analysis Cancer research High 23722546
2014 FABP5 controls brain anandamide (AEA) disposition through two mechanisms: (1) it promotes hydrolysis of AEA into arachidonic acid (reducing endocannabinoid levels) and (2) it directly shuttles arachidonic acid to the nucleus where it delivers it to PPARβ/δ for activation. Ablation of FABP5 in mice causes excess AEA accumulation, abolishes PPARβ/δ activation in the brain, and markedly impairs hippocampus-based learning and memory. FABP5 knockout mice, AEA quantification, PPARβ/δ target gene expression, behavioral testing (hippocampus-dependent tasks) The Journal of biological chemistry High 24644281
2021 FABP5 is susceptible to S-glutathionylation at Cys127 under oxidative conditions. This modification promotes FABP5's fatty acid binding ability and nuclear translocation, and promotes interaction of FABP5 with PPARβ/δ, activating PPARβ/δ target genes and suppressing LPS-induced inflammation in macrophages. The deglutathionylation enzyme Grx1 reverses this modification. Quantitative redox proteomics, site-directed mutagenesis (Cys127), nuclear fractionation, co-immunoprecipitation of FABP5-PPARβ/δ, Grx1 KO and conditional KO mice (Grx1fl/flLysMcre) Nature communications High 34876574
2010 FABP5 regulates keratinocyte differentiation via 13(S)-HODE-mediated NF-κB activation. FABP5 facilitates incorporation of linoleic acid into cells; linoleic acid is then metabolized to 13(S)-HODE, which induces keratin 1 expression concomitant with increased NF-κB activity. E-FABP(-/-) keratinocytes show decreased 13(S)-HODE levels, reduced NF-κB activity, and decreased keratin 1 expression. E-FABP knockout mice, linoleic acid incorporation assays, 13(S)-HODE quantification, NF-κB reporter assays, keratinocyte differentiation markers The Journal of investigative dermatology High 21068754
2014 E-FABP (FABP5) is highly expressed in macrophages and promotes antitumor activity by upregulating lipid droplet formation in response to tumors, leading to high IFN-β production. E-FABP-mediated IFN-β signaling enhances recruitment of NK cells to the tumor stroma. E-FABP KO mice, tumor-associated macrophage isolation, lipid droplet staining, IFN-β ELISA, NK cell recruitment assays, mammary tumor implantation model Cancer research Medium 24713431
2020 FABP5 is a binding partner of HIF-1α, identified by proteomics. FABP5 enhances HIF-1α activity by promoting HIF-1α synthesis while disrupting FIH/HIF-1α interaction. Oleic acid treatment activates the FABP5/HIF-1α axis, promoting lipid accumulation and cell proliferation in hepatocellular carcinoma cells. Co-immunoprecipitation proteomics to identify HIF-1α binding partners, FABP5 knockdown/overexpression, HIF-1α translation assay, FIH competitive binding assay, lipid accumulation measurement Communications biology Medium 33128030
2019 FABP5 acts as a central lipid chaperone linking cytosolic fatty acid metabolism (generated by FASN and MAGL) to pro-metastatic nuclear receptor signaling in prostate cancer. The pro-metastatic effects of FASN and MAGL are critically dependent on co-expression of FABP5 both in vitro and in vivo. ShRNA knockdown of FABP5, FASN, MAGL combinations; nuclear receptor activation assays; in vivo xenograft metastasis models Scientific reports Medium 31831821
2018 FABP5 promotes lipolysis of lipid droplets, de novo fatty acid synthesis, and NF-κB signaling in cancer cells. FABP5 knockdown downregulates HSL, MAGL, Elovl6, and ACSL1. FABP5 activates NF-κB through reactive oxygen species and protein kinase C. siRNA knockdown in prostate and breast cancer cells, gene expression analysis, ROS measurement, PKC activity assays, NF-κB reporter assays Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 29906613
2022 FABP5 selectively programs long-chain unsaturated fatty acid (particularly oleic acid) metabolism in macrophages. Fabp5 deletion causes accumulation of free long-chain unsaturated FAs; the mechanism involves enhanced FA β-oxidation, TCA cycle, and oxidative phosphorylation via activation of PPARγ signaling, reshaping macrophages toward M2 polarization. Myeloid-specific FABP5 conditional KO mice, OVA-induced allergic airway inflammation model, in vitro M2 polarization assays, lipidomics, metabolic flux analysis, PPARγ signaling readouts Cell reports Medium 36384126
2022 FABP5 deletion in macrophages increases intracellular unsaturated fatty acids (especially oleic acid), which increases the AMP/ATP ratio and activates AMPK, thereby inhibiting the NF-κB pathway and reducing macrophage inflammatory responses. Pharmacological AMPK inhibition rescued the decreased NF-κB signaling in FABP5-KO macrophages. Myeloid-specific FABP5 KO mice, LPS-induced acute liver injury model, RNA-sequencing, AMP/ATP ratio measurement, AMPK activation assays, NF-κB pathway analysis, pharmacological rescue with AMPK inhibitor Journal of immunology Medium 36426981
2025 FABP5 directly binds to Raptor (the regulatory-associated protein of mTOR) to enhance formation of functional mTORC1 and substrate binding, activated by ω-6 linoleic acid. This constitutes a direct nutrient-sensing mechanism linking dietary linoleic acid to mTORC1 activation and cell proliferation. Co-immunoprecipitation of FABP5-Raptor, in vitro binding assays, mTORC1 activity assays, FABP5 KO cells, FABP5-linoleic acid binding assessment Science High 40080571
2022 Activated keratinocytes produce chemokines and cytokines that trigger neutrophil chemotaxis in an FABP5-dependent manner. Mechanistically, FABP5 interacts with valosin-containing protein (VCP), a key player in NF-κB signaling. Silencing of FABP5, VCP, or both inhibits NF-κB/neutrophil chemotaxis signaling. Keratinocyte-specific (Krt6a-Cre) but not myeloid-specific (LysM-Cre) FABP5 deletion attenuates psoriatic symptoms. Global and conditional KO mice (Krt6a-Cre, LysM-Cre), proteomic analysis identifying FABP5-VCP interaction, Co-IP, siRNA silencing of FABP5 and VCP, NF-κB reporter assays, neutrophil chemotaxis assays Cell reports High 37967009
2024 Long-chain unsaturated fatty acids (UFAs) released by tumor cells activate PPARγ via FABP5 in tumor-associated macrophages (TAMs), resulting in immunosuppressive properties. FABP5 deficiency in macrophages decreases immunosuppressive molecule expression and enhances T cell-dependent antitumor immunity. Macrophage-specific FABP5 KO mice, single-cell RNA sequencing, in vitro UFA stimulation of macrophages, PPARγ signaling readouts, tumor growth assays Journal of hepatology Medium 39357545
2017 FABP5 overexpression in human fibroblasts causes nuclear translocation of SMAD2 and significant activation of the TGF-β signaling pathway, promoting profibrotic gene expression. Exogenous FABP5-EGFP can be incorporated by skin cells and intensify TGF-β signaling. FABP5 overexpression in WS1 fibroblasts, immunofluorescence of SMAD2 nuclear localization, TGF-β target gene expression, exogenous FABP5-EGFP uptake Radiation research Medium 29215326
2015 FABP5 overexpression in prostate cancer is caused by hypomethylation of a CpG island in its promoter region, coupled with upregulation of direct trans-acting transcription factors Sp1 and c-Myc. Silencing Sp1, c-Myc, or FABP5 significantly decreases cancer cell proliferation. Bisulfite sequencing, COBRA, qAMP methylation analysis; Sp1 and c-Myc siRNA knockdown; proliferation assays The Biochemical journal Medium 26614767
2013 E-FABP (FABP5) induces differentiation markers (K10, involucrin) in normal human keratinocytes. E-FABP inhibition by siRNA downregulates K10 and involucrin through NF-κB and JNK signaling pathways. Recombinant E-FABP transfection, siRNA knockdown, differentiation marker expression (K10, involucrin), NF-κB and JNK pathway assays Experimental dermatology Medium 23528210
2008 E-FABP binds a broad range of saturated and unsaturated long-chain fatty acids including DHA, EPA, and arachidonic acid. E-FABP expression is required for normal neurite extension in NGF-differentiated PC12 cells; antisense knockdown reduces neurite number/length, and replenishment with recombinant E-FABP restores neurite outgrowth. E-FABP localizes to cytoplasm and nuclear regions of neurons. FABP radiobinding analysis, antisense PC12 clones, recombinant E-FABP protein rescue, neurite measurement, subcellular fractionation/immunofluorescence Journal of neurochemistry Medium 18513372
2014 FABP5 promotes intracellular transport and inactivation of endocannabinoids (including anandamide) in intestinal K cells. FABP5-deficient mice have significantly decreased circulating GIP levels in the fasting state and in response to acute oral fat diet administration, establishing FABP5 as a regulator of GIP secretion via endocannabinoid control. FABP5-KO mice, GIP-GFP reporter knock-in mice, RNA-seq of purified K cells, GIP ELISA from plasma after fat challenge Molecular endocrinology Medium 25268051
2022 FABP5 deletion specifically in TRPV1+ nociceptors augments anandamide levels, producing antinociceptive effects mediated by CB1. Mechanistically, FABP5 deletion suppresses inflammation- and NGF-mediated TRPV1 sensitization via CB1 through calcineurin. FABP5 functions as an intracellular AEA carrier to FAAH for inactivation in nociceptors. Conditional FABP5 KO (TRPV1-Cre), anandamide quantification, TRPV1 sensitization assays (capsaicin, NGF), CB1 antagonist pharmacology, calcineurin inhibitor studies, FAAH inhibitor comparison Scientific reports High 35655086
1999 E-FABP (FABP5) and S100A7 form a complex in the cytosol of human keratinocytes. Gel filtration and non-denaturing PAGE showed S100A7 co-purifies with E-FABP; co-immunoprecipitation confirmed their association in protein extracts from psoriatic scales. Gel filtration chromatography, non-denaturing PAGE, co-immunoprecipitation from psoriatic keratinocyte extracts Molecular and cellular biochemistry Medium 10331666
2009 FABP5 knockdown in RPE cells decreases cholesterol and cholesterol ester levels by ~40%, increases triglycerides by 67%, and decreases apoB100 secretion by 76%, demonstrating that FABP5 plays a critical role in lipid metabolism and lipoprotein particle formation in retinal pigment epithelial cells. siRNA knockdown in ARPE-19 cells, lipid class quantification, apoB100 ELISA, lipoprotein secretion assay Laboratory investigation Medium 19434059
2012 Both FABP7 and FABP5 are required for normal proliferation and differentiation of neural stem/progenitor cells in the postnatal hippocampal dentate gyrus. FABP5 KO reduces the number of mature oligodendrocytes with membrane sheet morphology, and FABP7/FABP5 double KO dramatically reduces NSC/NPC numbers while increasing survival of BrdU+ cells and enhancing neuronal differentiation. Single and double FABP KO mice, BrdU incorporation and survival tracking, immunofluorescent staging of NSC/NPC differentiation markers Stem cells Medium 22581784
2002 E-FABP KO mice show impaired recovery of transepidermal water loss (TEWL) after skin lipid barrier disruption by acetone, with lower basal TEWL. H-FABP expression is specifically elevated in liver of neonatal heterozygous and homozygous mice, suggesting functional compensation by H-FABP for E-FABP deficiency. E-FABP KO mice, TEWL measurement after acetone treatment, Northern blot for compensatory FABP expression Molecular and cellular biochemistry Medium 12479572
2021 FABP5 co-localizes with α-synuclein (αSyn) in mitochondria under oxidative stress (rotenone treatment), reducing mitochondrial membrane potential and promoting cell death. Pharmacological inhibition of FABP5 prevented αSyn accumulation in mitochondria and rescued cell viability. Co-overexpression of FABP5 and αSyn in Neuro-2A cells, rotenone treatment, co-localization immunofluorescence, mitochondrial membrane potential assay, FABP5 pharmacological inhibitor rescue Biomedicines Medium 33499263
2019 Palmitate acid promotes nuclear transport of FABP5, which then increases nuclear SP1 protein levels, consequently increasing UCA1 expression in gastric cancer cells and promoting metastatic properties. Immunofluorescence of FABP5 nuclear translocation after PA treatment, siRNA knockdown of FABP5 and SP1, Western blot, RT-PCR for UCA1, migration/invasion assays Cancer cell international Medium 30948929
2013 FABP5 modulates PPARγ activity in airway epithelial cells; FABP5 overexpression increases expression of β-defensin-2 and limits IL-8 production against Pseudomonas aeruginosa infection. FABP5 knockdown increases bacterial load and inflammatory cytokine production. FABP5 exerts protective immunomodulatory functions through modulation of PPARγ activity. FABP5 knockdown and overexpression in primary NHBE cells, P. aeruginosa infection assay, β-defensin-2 and IL-8 quantification, PPARγ activity assay, cigarette smoke exposure PloS one Medium 23349676
2021 FABP5 deficiency in cardiac fibroblasts increases oxidative stress, reduces mitochondrial respiration, and increases myofibroblast activation markers in response to TGF-β. In FABP5 KO mice with TAC-induced cardiac remodeling, FABP5 deficiency aggravates cardiac hypertrophy, fibrosis, and mitochondrial impairment. FABP5 global KO mice with TAC surgery, echocardiography, transmission electron microscopy, ATP detection, siRNA in primary cardiac fibroblasts, mitochondrial respiration assay, oxidative stress assay Cardiovascular toxicology Medium 33929718
2010 FABP5 knockdown in 3T3-L1 preadipocytes during adipocytic induction triggers apoptosis via caspase-3 activation and reduces expression of PPARγ and C/EBPα. FABP5 is required for preadipocyte viability during adipogenesis through activation of the Akt cascade. siRNA knockdown in 3T3-L1 cells during adipogenic induction, caspase-3 activity assay, procaspase-3 cleavage, PPARγ/C/EBPα Western blot, Akt phosphorylation assay Molecular biology reports Medium 20238174
2024 MELK kinase binds to FABP5 and stabilizes it by affecting its ubiquitination through the K48R pathway, thereby activating the Akt/mTOR signaling axis in HCC cells. Co-immunoprecipitation of MELK-FABP5, ubiquitination assay identifying K48-linked ubiquitin chain modification, Akt/mTOR pathway readouts, MELK knockdown Military Medical Research Medium 39871325
2024 TRIM45 E3 ligase directly adds K33-type and K63-type poly-ubiquitin chains to the NLS domain of FABP5, promoting FABP5 nuclear translocation. Nuclear FABP5 then interacts with PPARγ to facilitate downstream lipid synthesis gene expression. IP-tandem mass spectrometry identifying TRIM45-FABP5 interaction, ubiquitin linkage-specific assay (K33/K63), nuclear fractionation, FABP5-PPARγ Co-IP, gene expression of lipid synthesis targets Oncogene Medium 38755308
2025 Asprosin interacts with FABP5, and this interaction facilitates abnormal nuclear localization of asprosin. Nuclear asprosin directly binds to and inhibits PPARα transcriptional activity at PPRE elements, disrupting hepatic fatty acid β-oxidation. GalNAc-siRNA targeting hepatic FABP5 ameliorates hepatic steatosis in MASLD. Co-IP of asprosin-FABP5, nuclear fractionation, PPRE reporter assay, ChIP for asprosin at PPREs, hepatocyte-specific asprosin overexpression/knockdown, GalNAc-siRNA targeting FABP5 Advanced science Medium 40231957
2023 FABP5 interacts with fatty acid synthase (FASN) and promotes FASN degradation through the ubiquitin proteasome pathway, leading to decreased FASN expression, reduced lipid accumulation, and suppression of mTOR signaling to facilitate autophagy in colorectal cancer cells. Co-immunoprecipitation of FABP5-FASN, ubiquitin proteasome pathway assay, mTOR signaling readouts, autophagy assays, FABP5 KO/overexpression in CRC cells International journal of biological sciences Medium 37416772
2023 FABP5 interacts with FASN in pancreatic neuroendocrine neoplasm cells and regulates FASN expression via the ubiquitin proteasome pathway. FABP5 promotes lipid droplet deposition and activates the WNT/β-catenin signaling pathway to facilitate pNEN progression. Co-immunoprecipitation of FABP5-FASN, ubiquitin proteasome pathway assay, lipid droplet staining, WNT/β-catenin reporter assays, FABP5 knockdown/overexpression Cancer science Medium 37302809
2022 FABP5 in macrophage monocytes activates FABP5 expression and decreases β-oxidation, causing lipid droplet accumulation. This FABP5-mediated lipid accumulation increases IL-10 secretion by suppressing the PPARα pathway. The elevated IL-10 then promotes PD-L1 expression on Treg cells via JNK-STAT3 pathway activation, fostering immune tolerance in HCC. FABP5 knockdown in monocytes, β-oxidation assay, lipid droplet staining, IL-10 ELISA, PPARα pathway analysis, PD-L1 expression on Tregs, JNK-STAT3 signaling Cancer gene therapy Low 35902729
2021 E-FABP (FABP5) expressed in T cells facilitates linoleic acid (LA) mitochondrial transport and cardiolipin incorporation. LA induces mitochondrial ROS production and lipid peroxidation in T cells; E-FABP genetic depletion rescues LA-impaired T-cell responses and suppresses LA-rich HFD-associated mammary tumor growth. E-FABP KO mice on high-fat diet, LA/OA fatty acid uptake comparison, mitochondrial ROS measurement, cardiolipin incorporation assay, T cell apoptosis and TNFα production assays, tumor growth Cancer research Medium 34400394
2025 GPR171 deficiency promotes Th17 cell differentiation and alters lipidome via the cAMP-pCREB-FABP5 axis. Blockade of FABP5 reduces Th17 cell differentiation in vitro and ameliorates DSS-induced colitis in Gpr171-/- mice, placing FABP5 downstream of GPR171/cAMP/pCREB in Th17 differentiation. GPR171 KO mice, BigLEN ligand treatment, cAMP/pCREB pathway analysis, FABP5 inhibitor treatment, RNA-seq, lipidomics, DSS colitis model with Gpr171-/- background Gut Medium 40074327
2019 Lysine enhances fatty acid-stimulated milk fat synthesis through GPRC6A-PI3K-FABP5 signaling in bovine mammary epithelial cells. Lysine stimulates FABP5 expression via GPRC6A-PI3K signaling, and FABP5 in turn enhances SREBP-1c expression and maturation to drive milk fat synthesis. siRNA knockdown of FABP5 and GPRC6A, PI3K inhibitor treatment, SREBP-1c maturation assay, lipid droplet/milk fat quantification in BMECs Journal of agricultural and food chemistry Medium 31174423
2024 The FABP5 inhibitor ART26.12 selectively binds FABP5 compared to FABP3, FABP4, and FABP7, and produces CB1-dependent anti-allodynic effects in an oxaliplatin-induced peripheral neuropathy model; spinal cord lipidomics revealed widespread lipid modulation including N-acyl amino acids. Binding selectivity (MST/fluorescence), CB1 antagonist pharmacology, OIPN mouse model with acute and repeated dosing, multi-scale lipidomics of spinal cord The journal of pain Medium 38232863
2024 Fatty acid binding properties of FABP5 characterized by EPR spectroscopy: FABP5 shows two distinct binding states ('intermediately' and 'strongly' bound) for fatty acid ligands; the proportion and dynamics of binding depend on FABP concentration and temperature, with the more dynamic 'intermediately bound' state dominating at body temperature. CW-EPR spectroscopy with spin-labeled fatty acids (5/16-DOXYL stearic acid), microscale thermophoresis, dynamic light scattering, EPR spectral simulation The Journal of biological chemistry Medium 38777142

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins. The Journal of investigative dermatology 225 1512466
2017 Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases. Pharmacology & therapeutics 199 28132904
2020 Fatty-acid-induced FABP5/HIF-1 reprograms lipid metabolism and enhances the proliferation of liver cancer cells. Communications biology 194 33128030
2021 Oxidative stress-induced FABP5 S-glutathionylation protects against acute lung injury by suppressing inflammation in macrophages. Nature communications 153 34876574
2020 FABP5 promotes lymph node metastasis in cervical cancer by reprogramming fatty acid metabolism. Theranostics 143 32550890
2014 Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages. Cancer research 115 24713431
2014 Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor β/δ (FABP5-PPARβ/δ) signaling pathway. The Journal of biological chemistry 104 24692551
2018 Fatty acid-binding protein 5 (FABP5) promotes lipolysis of lipid droplets, de novo fatty acid (FA) synthesis and activation of nuclear factor-kappa B (NF-κB) signaling in cancer cells. Biochimica et biophysica acta. Molecular and cell biology of lipids 103 29906613
2013 Genetic ablation of the fatty acid-binding protein FABP5 suppresses HER2-induced mammary tumorigenesis. Cancer research 95 23722546
2012 The effects of Fabp7 and Fabp5 on postnatal hippocampal neurogenesis in the mouse. Stem cells (Dayton, Ohio) 93 22581784
1993 Characterization and expression of a novel human fatty acid-binding protein: the epidermal type (E-FABP). Biochemical and biophysical research communications 87 8427590
2010 Epidermal FABP (FABP5) regulates keratinocyte differentiation by 13(S)-HODE-mediated activation of the NF-κB signaling pathway. The Journal of investigative dermatology 84 21068754
2014 Fatty acid-binding protein 5 (FABP5) regulates cognitive function both by decreasing anandamide levels and by activating the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) in the brain. The Journal of biological chemistry 82 24644281
2023 NSUN2 promotes osteosarcoma progression by enhancing the stability of FABP5 mRNA via m5C methylation. Cell death & disease 77 36792587
2022 FABP5 controls macrophage alternative activation and allergic asthma by selectively programming long-chain unsaturated fatty acid metabolism. Cell reports 70 36384126
2019 FABP5 coordinates lipid signaling that promotes prostate cancer metastasis. Scientific reports 67 31831821
2022 m6A-induced lncDBET promotes the malignant progression of bladder cancer through FABP5-mediated lipid metabolism. Theranostics 64 36168624
2024 FABP5+ lipid-loaded macrophages process tumour-derived unsaturated fatty acid signal to suppress T-cell antitumour immunity. Journal of hepatology 62 39357545
2023 The emerging role of fatty acid binding protein 5 (FABP5) in cancers. Drug discovery today 61 37230284
2004 The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP. Cancer letters 58 15922867
2023 FABP5 suppresses colorectal cancer progression via mTOR-mediated autophagy by decreasing FASN expression. International journal of biological sciences 56 37416772
2019 Lysine Enhances the Stimulation of Fatty Acids on Milk Fat Synthesis via the GPRC6A-PI3K-FABP5 Signaling in Bovine Mammary Epithelial Cells. Journal of agricultural and food chemistry 56 31174423
2015 The cancer-promoting gene fatty acid-binding protein 5 (FABP5) is epigenetically regulated during human prostate carcinogenesis. The Biochemical journal 55 26614767
2020 Identification of FABP5 as an immunometabolic marker in human hepatocellular carcinoma. Journal for immunotherapy of cancer 54 32611686
2013 E-FABP induces differentiation in normal human keratinocytes and modulates the differentiation process in psoriatic keratinocytes in vitro. Experimental dermatology 54 23528210
2008 Expression of E-FABP in PC12 cells increases neurite extension during differentiation: involvement of n-3 and n-6 fatty acids. Journal of neurochemistry 53 18513372
2021 CCAT1/FABP5 promotes tumour progression through mediating fatty acid metabolism and stabilizing PI3K/AKT/mTOR signalling in lung adenocarcinoma. Journal of cellular and molecular medicine 52 34431227
2019 FABP5 regulates the proliferation of clear cell renal cell carcinoma cells via the PI3K/AKT signaling pathway. International journal of oncology 52 30968158
2002 Analysis on the phenotype of E-FABP-gene knockout mice. Molecular and cellular biochemistry 52 12479572
2022 Lipid-related FABP5 activation of tumor-associated monocytes fosters immune privilege via PD-L1 expression on Treg cells in hepatocellular carcinoma. Cancer gene therapy 46 35902729
2017 Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3-M cells by competitively binding to oncogenic FABP5. Oncotarget 44 28415688
2021 Dietary Fats High in Linoleic Acids Impair Antitumor T-cell Responses by Inducing E-FABP-Mediated Mitochondrial Dysfunction. Cancer research 43 34400394
2013 FABP5 deficiency enhances susceptibility to H1N1 influenza A virus-induced lung inflammation. American journal of physiology. Lung cellular and molecular physiology 42 23624787
2000 In situ and immunocytochemical localization of E-FABP mRNA and protein during neuronal migration and differentiation in the rat brain. Brain research 42 10661491
2020 Deregulating the CYP2C19/Epoxy-Eicosatrienoic Acid-Associated FABP4/FABP5 Signaling Network as a Therapeutic Approach for Metastatic Triple-Negative Breast Cancer. Cancers 40 31941087
2013 Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells. Cell and tissue research 40 24114376
2017 The Role of FABP5 in Radiation-Induced Human Skin Fibrosis. Radiation research 39 29215326
2002 Solution structure and backbone dynamics of human epidermal-type fatty acid-binding protein (E-FABP). The Biochemical journal 39 12049637
2000 PA-FABP, a novel marker of human epidermal transit amplifying cells revealed by 2D protein gel electrophoresis and cDNA array hybridisation. FEBS letters 39 11113456
2024 Hypoxic tumor-derived exosomal miR-4488 induces macrophage M2 polarization to promote liver metastasis of pancreatic neuroendocrine neoplasm through RTN3/FABP5 mediated fatty acid oxidation. International journal of biological sciences 38 38904015
2017 Serum FABP5 concentration is a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages. Scientific reports 36 28303004
2025 Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling. Science (New York, N.Y.) 34 40080571
2013 Cigarette smoke decreases airway epithelial FABP5 expression and promotes Pseudomonas aeruginosa infection. PloS one 34 23349676
2008 The evolutionary relationship between the duplicated copies of the zebrafish fabp11 gene and the tetrapod FABP4, FABP5, FABP8 and FABP9 genes. The FEBS journal 34 18445037
2023 ALKBH5 enhances lipid metabolism reprogramming by increasing stability of FABP5 to promote pancreatic neuroendocrine neoplasms progression in an m6A-IGF2BP2-dependent manner. Journal of translational medicine 33 37858219
2023 Doxorubicin resistance in breast cancer is mediated via the activation of FABP5/PPARγ and CaMKII signaling pathway. Frontiers in pharmacology 32 37538178
2022 FABP5 Deficiency Impaired Macrophage Inflammation by Regulating AMPK/NF-κB Signaling Pathway. Journal of immunology (Baltimore, Md. : 1950) 32 36426981
2021 FABP5 enhances malignancies of lower-grade gliomas via canonical activation of NF-κB signaling. Journal of cellular and molecular medicine 31 33837625
1999 Probable interaction between S100A7 and E-FABP in the cytosol of human keratinocytes from psoriatic scales. Molecular and cellular biochemistry 31 10331666
2015 Level of Fatty Acid Binding Protein 5 (FABP5) Is Increased in Sputum of Allergic Asthmatics and Links to Airway Remodeling and Inflammation. PloS one 30 26020772
2006 Characterization of the porcine FABP5 gene and its association with the FAT1 QTL in an Iberian by Landrace cross. Animal genetics 30 17121606
2016 Transcriptome and Metabolome Analyses in Exogenous FABP4- and FABP5-Treated Adipose-Derived Stem Cells. PloS one 29 27936164
2010 SiRNA against Fabp5 induces 3T3-L1 cells apoptosis during adipocytic induction. Molecular biology reports 29 20238174
2006 Metastasis of squamous cell carcinoma of the oral tongue is associated with down-regulation of epidermal fatty acid binding protein (E-FABP). Oral oncology 29 16759896
2023 Role of FABP5 in T Cell Lipid Metabolism and Function in the Tumor Microenvironment. Cancers 28 36765614
2023 FABP5 regulates lipid metabolism to facilitate pancreatic neuroendocrine neoplasms progression via FASN mediated Wnt/β-catenin pathway. Cancer science 28 37302809
2019 Inactivated FABP5 suppresses malignant progression of prostate cancer cells by inhibiting the activation of nuclear fatty acid receptor PPARγ. Genes & cancer 28 31258834
2019 Pterostilbene Inhibits Adipocyte Conditioned-Medium-Induced Colorectal Cancer Cell Migration through Targeting FABP5-Related Signaling Pathway. Journal of agricultural and food chemistry 28 31419115
2021 FABP5 Deficiency Impairs Mitochondrial Function and Aggravates Pathological Cardiac Remodeling and Dysfunction. Cardiovascular toxicology 27 33929718
2010 Atelocollagen-delivered siRNA targeting the FABP5 gene as an experimental therapy for prostate cancer in mouse xenografts. International journal of oncology 27 19956834
2021 Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress. Biomedicines 26 33499263
2020 FABP5 as a possible biomarker in atopic march: FABP5-induced Th17 polarization, both in mouse model and human samples. EBioMedicine 26 32711257
2022 Accumulation of systematic TPM1 mediates inflammation and neuronal remodeling by phosphorylating PKA and regulating the FABP5/NF-κB signaling pathway in the retina of aged mice. Aging cell 24 35148456
2020 Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus. Frontiers in endocrinology 24 33071982
2019 Palmitate acid promotes gastric cancer metastasis via FABP5/SP1/UCA1 pathway. Cancer cell international 24 30948929
2009 Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100 secretion and triglyceride accumulation in ARPE-19 cells. Laboratory investigation; a journal of technical methods and pathology 24 19434059
2025 MELK prevents radiofrequency ablation-induced immunogenic cell death and antitumor immune response by stabilizing FABP5 in hepatocellular malignancies. Military Medical Research 22 39871325
2022 FABP5 deletion in nociceptors augments endocannabinoid signaling and suppresses TRPV1 sensitization and inflammatory pain. Scientific reports 22 35655086
2017 Effect of FABP5 gene silencing on the proliferation, apoptosis and invasion of human gastric SGC-7901 cancer cells. Oncology letters 22 29085478
2011 CRABP-II- and FABP5-independent all-trans retinoic acid resistance in COLO 16 human cutaneous squamous cancer cells. Experimental dermatology 22 22082219
2019 DHA and vitamin E antagonized the Aβ25-35-mediated neuron oxidative damage through activation of Nrf2 signaling pathways and regulation of CD36, SRB1 and FABP5 expression in PC12 cells. Food & function 21 30706921
2014 Expression of epidermal fatty acid binding protein (E-FABP) in septoclasts in the growth plate cartilage of mice. Journal of molecular histology 21 24879443
2014 RNA-Seq analysis of enteroendocrine cells reveals a role for FABP5 in the control of GIP secretion. Molecular endocrinology (Baltimore, Md.) 21 25268051
2024 Discovery and Preclinical Evaluation of a Novel Inhibitor of FABP5, ART26.12, Effective in Oxaliplatin-Induced Peripheral Neuropathy. The journal of pain 20 38232863
2021 Downregulation of FABP5 Suppresses the Proliferation and Induces the Apoptosis of Gastric Cancer Cells Through the Hippo Signaling Pathway. DNA and cell biology 20 34160301
2023 Keratinocyte FABP5-VCP complex mediates recruitment of neutrophils in psoriasis. Cell reports 19 37967009
2021 Tumor-intrinsic FABP5 is a novel driver for colon cancer cell growth via the HIF-1 signaling pathway. Cancer genetics 19 34775260
1997 Skin-derived antileukoproteinase (SKALP) and epidermal fatty acid-binding protein (E-FABP): two novel markers of the psoriatic phenotype that respond differentially to topical steroid. Acta dermato-venereologica 19 9059669
2012 Fatty acid-binding protein 4 (FABP4) and FABP5 modulate cytokine production in the mouse thymic epithelial cells. Histochemistry and cell biology 18 22585040
2024 TRIM45 facilitates NASH-progressed HCC by promoting fatty acid synthesis via catalyzing FABP5 ubiquitylation. Oncogene 17 38755308
2021 FABP5 Is a Sensitive Marker for Lipid-Rich Macrophages in the Luminal Side of Atherosclerotic Lesions. International heart journal 17 33994513
2020 Circ-ABCB10 acts as an oncogene in glioma cells via regulation of the miR-620/FABP5 axis. European review for medical and pharmacological sciences 17 32633377
2015 CRABP-II- and FABP5-independent responsiveness of human glioblastoma cells to all-trans retinoic acid. Oncotarget 17 25797252
2023 FAM201A encodes small protein NBASP to inhibit neuroblastoma progression via inactivating MAPK pathway mediated by FABP5. Communications biology 15 37438449
2018 4-Amino-2-trifluoromethyl-phenyl retinate inhibits proliferation, invasion, and migration of breast cancer cells by independently regulating CRABP2 and FABP5. Drug design, development and therapy 14 29731607
2017 Retinoic acid regulates cell-shape and -death of E-FABP (FABP5)-immunoreactive septoclasts in the growth plate cartilage of mice. Histochemistry and cell biology 14 28500502
2022 Environmental enrichment sex-dependently rescues memory impairment in FABP5 KO mice not mediated by brain-derived neurotrophic factor. Behavioural brain research 13 35202717
2022 Topical VX-509 attenuates psoriatic inflammation through the STAT3/FABP5 pathway in keratinocytes. Pharmacological research 13 35728766
2021 Serum fatty acid binding protein 5 (FABP5) as a potential biomarker of inflammation in psoriasis. Molecular biology reports 13 34131888
2019 Fatty acid-binding protein 5 (FABP5)-related signal transduction pathway in castration-resistant prostate cancer cells: a potential therapeutic target. Precision clinical medicine 13 35694437
2008 Nucleotide variability and linkage disequilibrium patterns at the porcine FABP5 gene. Animal genetics 13 18565161
2025 GPR171 restrains intestinal inflammation by suppressing FABP5-mediated Th17 cell differentiation and lipid metabolism. Gut 12 40074327
2025 Asprosin-FABP5 Interaction Modulates Mitochondrial Fatty Acid Oxidation through PPARα Contributing to MASLD Development. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 40231957
2024 Fatty acid binding to the human transport proteins FABP3, FABP4, and FABP5 from a Ligand's perspective. The Journal of biological chemistry 12 38777142
2024 Artesunate-binding FABP5 promotes apoptosis in lung cancer cells via the PPARγ-SCD pathway. International immunopharmacology 12 39405934
2023 Time-resolved single-cell RNAseq profiling identifies a novel Fabp5+ subpopulation of inflammatory myeloid cells with delayed cytotoxic profile in chronic spinal cord injury. Heliyon 12 37636454
2023 FABP5 is important for cognitive function and is an important regulator of the physiological effects and pharmacokinetics of acute Δ9 tetrahydrocannabinol inhalation in mice. Pharmacology, biochemistry, and behavior 12 37716413
2023 Inhibition of FABP5 attenuates inflammatory bowel disease by modulating macrophage alternative activation. Biochemical pharmacology 12 38081366
2023 FABP5 Inhibition against PTEN-Mutant Therapy Resistant Prostate Cancer. Cancers 12 38201488
2013 Circulating FABP4 and FABP5 levels are differently linked to OSA severity and treatment. Sleep 12 24293757

Missed literature

Know a paper Affinage missed for FABP5? Flag it for the maintainers and the community.

No submissions yet.