Affinage

ABHD6

Monoacylglycerol lipase ABHD6 · UniProt Q9BV23

Length
337 aa
Mass
38.3 kDa
Annotated
2026-06-09
51 papers in source corpus 19 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABHD6 is a membrane-bound serine hydrolase that shapes lipid signaling across neuronal, immune, and metabolic compartments while doubling as a hydrolase-independent regulator of glutamate receptor trafficking (PMID:20657592, PMID:27114538). Its catalytic triad centers on S148, with D278 and H306 completing an active site whose integrity is required for activity and for active-site probe labeling (PMID:22969151). As a 2-arachidonoylglycerol (2-AG) hydrolase, it limits endocannabinoid tone: inhibition raises activity-dependent 2-AG to enable CB1-dependent long-term depression and CB2-mediated microglial migration, and routes 2-AG toward COX-2-derived anti-inflammatory PGD2-glycerol esters (PMID:20657592, PMID:24101490). ABHD6 also degrades the lysosomal lipid bis(monoacylglycero)phosphate (BMP), accounting for most hepatic BMP hydrolase activity, with loss of function altering circulating BMP in mice and humans (PMID:26491015, PMID:30894461), and serves as a major lysophosphatidylserine lipase in liver and kidney (PMID:39761854). Through control of monoacylglycerol (MAG) pools it gates PPARα/γ signaling governing adipose thermogenesis, macrophage polarization, and NSCLC malignancy (PMID:33201859, PMID:32143183, PMID:37838014). In the brain it controls extrasynaptic tonic GABA_A receptor currents and, through a separable non-catalytic function, binds the C-terminal tails of GluA1–3 to suppress AMPAR surface delivery, drive activity-dependent AMPAR endocytosis, and—together with TARP γ-2—tune AMPAR gating, thereby supporting hippocampal LTD and synaptic downscaling (PMID:27114538, PMID:36990366, PMID:38159878). Its hydrolase activity is restrained by malonyl-CoA-sensing CPT1C, and in lenvatinib-resistant hepatocellular carcinoma K245 lactylation redirects ABHD6 to mitochondria where it scaffolds FIS1 and displaces DRP1 to suppress fission (PMID:33444462, PMID:41861279). Genetic and pharmacological loss of ABHD6 is protective in models of seizure, Dravet syndrome, autoimmune neuroinflammation, and diet-induced obesity (PMID:25033180, PMID:26189763, PMID:36990366, PMID:39681558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2010 High

    Established ABHD6 as a postsynaptic 2-AG hydrolase that sets endocannabinoid tone, answering whether 2-AG degradation is enzyme-controlled at synapses and in microglia.

    Evidence shRNA knockdown in BV-2 microglia, pharmacological inhibition with electrophysiology in neurons/slices, subcellular fractionation

    PMID:20657592

    Open questions at the time
    • Did not define the catalytic residues
    • Substrate scope beyond 2-AG unaddressed
  2. 2012 High

    Defined the catalytic machinery, confirming ABHD6 as a bona fide monoacylglycerol lipase with an S148-centered active site.

    Evidence Site-directed mutagenesis of S148/D278/H306, fluorescent glycerol assay, TAMRA-FP activity-based labeling, substrate profiling

    PMID:22969151

    Open questions at the time
    • Catalytic roles of D278 and H306 unconfirmed due to loss of expression
    • In vitro substrate ranking may not reflect cellular preference
  3. 2013 High

    Connected ABHD6 substrate control to downstream eicosanoid signaling, showing 2-AG it spares is oxygenated by COX-2 into anti-inflammatory PGD2-G.

    Evidence Sequential pharmacological blockade (ABHD6, COX-2, PGD synthase), lipid mass spectrometry, in vivo LPS inflammation

    PMID:24101490

    Open questions at the time
    • Receptor target of PGD2-G not identified
    • Macrophage-specific contribution vs systemic not resolved
  4. 2014 High

    Revealed a CB-receptor-independent antiepileptic mechanism, implicating GABA_A receptor signaling downstream of ABHD6 inhibition.

    Evidence Pharmacological inhibition in Cnr1-/- and Cnr2-/- mice with picrotoxin co-administration, seizure behavior

    PMID:25033180

    Open questions at the time
    • Molecular link from ABHD6 lipid product to GABA_A currents undefined
    • Cell type mediating the effect not pinpointed
  5. 2015 High

    Identified ABHD6 as a dominant BMP hydrolase, expanding its substrate range beyond MAGs into lysosomal lipid catabolism.

    Evidence BMP hydrolase assay, siRNA knockdown with lipidomics, tissue fractionation, live-cell imaging co-localization with late endosomes/lysosomes

    PMID:26491015

    Open questions at the time
    • How cytosolic ABHD6 accesses organelle-derived BMP not mechanistically shown
    • Physiological consequences of BMP accumulation not tested here
  6. 2015 Medium

    Tested ABHD6 inhibition in autoimmune neuroinflammation, attributing therapeutic benefit to CB2 signaling.

    Evidence WWL70 inhibition with CB1/CB2 antagonists and CB2-KO mice in EAE

    PMID:26189763

    Open questions at the time
    • WWL70 off-target effects complicate ABHD6 attribution
    • Single inhibitor without genetic ABHD6 loss
  7. 2016 High

    Uncovered a hydrolase-independent role: ABHD6 physically binds the GluA1 C-terminus to suppress AMPAR surface delivery, decoupling its enzymatic and synaptic functions.

    Evidence Overexpression and CRISPR KO in neurons, patch-clamp, surface biotinylation, pulldown, GFCLIPQ motif mutagenesis

    PMID:27114538

    Open questions at the time
    • Mechanism by which binding blocks delivery not defined
    • Whether the interaction is direct or scaffolded not fully resolved
  8. 2017 Medium

    Generalized the AMPAR interaction across subunits, showing ABHD6 binds GluA2 and GluA3 C-terminal domains to suppress their surface expression.

    Evidence HEK293T overexpression, patch-clamp, surface biotinylation, pulldown with C-terminal deletions

    PMID:28303090

    Open questions at the time
    • Subunit selectivity in native neurons not addressed
    • Single heterologous system
  9. 2019 High

    Validated ABHD6 as a physiologically relevant BMP hydrolase across species using genetic and human loss-of-function evidence.

    Evidence ABHD6 global KO mice with plasma/liver lipidomics, human loss-of-function patient

    PMID:30894461

    Open questions at the time
    • Clinical phenotype of altered BMP not characterized
    • Tissue source of circulating BMP unresolved
  10. 2020 Medium

    Placed ABHD6 upstream of PPAR-driven metabolic and oncogenic programs via control of MAG pools in adipose, lung cancer, and macrophages.

    Evidence Tissue-specific and global KO, overexpression, lipidomics, PPAR target/transactivation assays, xenograft and cold-tolerance models

    PMID:32143183 PMID:33201859 PMID:37838014

    Open questions at the time
    • Which MAG species directly engage PPARs not defined
    • Direct vs indirect PPAR activation not established
  11. 2020 Medium

    Identified transcriptional regulation of ABHD6 by the corepressor LSD1 during acute psychosocial stress, linking epigenetic control to endocannabinoid tone.

    Evidence Mouse stress models, gene expression, ChIP of LSD1 at Abhd6/Magl promoters

    PMID:32141088

    Open questions at the time
    • LSD1 cofactors at the Abhd6 promoter unknown
    • Loss of repression in chronic stress mechanistically unexplained
  12. 2021 High

    Defined post-translational/allosteric control of ABHD6 activity through CPT1C and malonyl-CoA sensing, coupling metabolic state to 2-AG/CB1 signaling.

    Evidence Reciprocal Co-IP, FRET, fluorescent activity assays in CPT1C-KO brain, cAMP CB1 assay, fasting manipulation

    PMID:33444462

    Open questions at the time
    • Structural basis of CPT1C-mediated inhibition unknown
    • Whether interaction modulates non-2AG substrates untested
  13. 2023 High

    Distinguished ABHD6 control of tonic versus phasic inhibition and demonstrated therapeutic benefit in Dravet syndrome via GABA_A potentiation.

    Evidence Abhd6+/- crossed with Scn1a+/-, inhibitor pharmacology, brain-slice electrophysiology of tonic/phasic GABA_A currents

    PMID:36990366

    Open questions at the time
    • Lipid product linking ABHD6 to extrasynaptic GABA_A receptors not identified
    • Granule-cell specificity vs other circuits not mapped
  14. 2023 High

    Showed ABHD6 is required for activity-dependent AMPAR endocytosis, LTD, and synaptic downscaling, establishing its non-catalytic role in plasticity and learning.

    Evidence ABHD6 KO mice, electrophysiology (LTD, mEPSC), AMPAR internalization assays, surface biotinylation, reversal learning

    PMID:38159878

    Open questions at the time
    • Endocytic machinery recruited by ABHD6 unidentified
    • Relationship to its lipid substrates not resolved
  15. 2024 High

    Localized a behaviorally decisive ABHD6 function to nucleus accumbens postsynaptic neurons controlling diet-induced obesity and reward-seeking.

    Evidence Three region-specific viral KD/KO approaches, electrophysiology of inhibitory transmission, behavior, intraventricular pharmacology

    PMID:39681558

    Open questions at the time
    • Substrate/pathway mediating MSN effect not defined
    • Hydrolase vs AMPAR-scaffold contribution to phenotype unseparated
  16. 2024 Medium

    Refined the AMPAR role by showing ABHD6 modulates gating kinetics conditionally on TARP γ-2, positioning it as an auxiliary subunit affecting receptor biophysics.

    Evidence Outside-out patches with ultra-fast glutamate application across AMPAR/TARP/ABHD6 combinations and ABHD6-KO neurons (preprint)

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Structural basis of the TARP-dependent effect unknown
  17. 2025 Medium

    Extended the substrate range to lysophosphatidylserine, designating ABHD6 the major lyso-PS lipase in liver and kidney distinct from brain ABHD12.

    Evidence Inhibitor screen against tissue membrane fractions, in vivo pharmacological validation, primary hepatocyte assays

    PMID:39761854

    Open questions at the time
    • Downstream lyso-PS signaling consequences untested
    • Genetic confirmation in vivo not provided
  18. 2026 Medium

    Revealed a lactylation-driven moonlighting function in which mitochondrial ABHD6 scaffolds FIS1, displaces DRP1, and confers cancer drug resistance independent of catalysis.

    Evidence K245 lactylation mapping, mitochondrial fractionation, ABHD6-FIS1 Co-IP, DRP1 displacement, S148 mutagenesis/occupancy, in vitro/in vivo resistance models

    PMID:41861279

    Open questions at the time
    • Single lab, not independently replicated
    • How an unoccupied S148 enables scaffolding unexplained
    • Lactyltransferase responsible not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ABHD6's distinct catalytic activities, its non-catalytic AMPAR-scaffolding function, and its lactylation-dependent mitochondrial role are integrated within a single protein and selected between in different cell types.
  • No structure of full-length ABHD6 with binding partners
  • Determinants directing ABHD6 to membrane substrates vs AMPAR vs mitochondria unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1 GO:0005764 lysosome 1 GO:0005768 endosome 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
CACNG2CPT1CFIS1GRIA1GRIA2GRIA3

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 ABHD6 is a postsynaptic serine hydrolase that hydrolyzes 2-arachidonoylglycerol (2-AG) and thereby controls its accumulation and efficacy at cannabinoid receptors. In BV-2 microglia, ABHD6 knockdown reduced 2-AG hydrolysis and increased CB2-mediated cell migration; in neurons, selective inhibition led to activity-dependent 2-AG accumulation and enabled CB1-dependent long-term depression by otherwise subthreshold stimulation. shRNA knockdown in BV-2 cells, pharmacological inhibition in primary neurons and cortical slices, electrophysiology (LTD induction), subcellular fractionation showing postsynaptic localization Nature neuroscience High 20657592
2012 Human ABHD6 is a genuine monoacylglycerol lipase with a catalytic triad comprising S148-D278-H306; site-directed mutagenesis of S148 abolished enzymatic activity and abolished labeling by the active-site serine-directed probe TAMRA-FP. Medium-chain saturated MAGs are the best substrates for hABHD6. Mutations of D278 and H306 abolished activity but also prevented detectable expression, so their direct catalytic roles could not be confirmed. Site-directed mutagenesis of catalytic triad residues, fluorescent glycerol activity assay, activity-based protein profiling (TAMRA-FP labeling), substrate profiling Journal of lipid research High 22969151
2013 In macrophages, ABHD6 controls 2-AG levels; pharmacological ABHD6 inhibition increases 2-AG, which is oxygenated by COX-2 to produce the anti-inflammatory prostaglandin D2-glycerol ester (PGD2-G). Blocking COX-2 or prostaglandin D synthase prevented the anti-inflammatory effects of ABHD6 inhibition, establishing a pathway: ABHD6 → 2-AG → COX-2 → PGD2-G → anti-inflammatory signaling. Pharmacological inhibition (ABHD6 inhibitor, COX-2 inhibitor, PGD synthase inhibitor), lipid mass spectrometry, in vivo LPS-inflammation model Proceedings of the National Academy of Sciences of the United States of America High 24101490
2014 ABHD6 inhibition decreases PTZ-induced seizures through a mechanism involving GABAA receptors (not CB1/CB2), as the antiepileptic effect was retained in Cnr1-/- and Cnr2-/- mice but blocked by a subconvulsive dose of the GABAA antagonist picrotoxin. Pharmacological inhibition, genetic knockout mice (Cnr1-/-, Cnr2-/-), picrotoxin co-administration, seizure behavioral assays Neuron High 25033180
2015 ABHD6 degrades bis(monoacylglycero)phosphate (BMP), a late endosomal/lysosomal lipid, with high specific activity. ABHD6 is responsible for ~90% of hepatic BMP hydrolase activity; ABHD6 knockdown increases hepatic BMP levels. Tissue fractionation and live-cell imaging showed ABHD6 co-localizes with late endosomes/lysosomes, and the enzyme is active at cytosolic pH, suggesting it degrades BMP exported from acidic organelles. BMP hydrolase activity assay, siRNA knockdown with lipidomics, tissue fractionation, live-cell imaging co-localization The Journal of biological chemistry High 26491015
2015 ABHD6 inhibition with WWL70 ameliorates experimental autoimmune encephalomyelitis (EAE) through a CB2 receptor-dependent mechanism: the therapeutic effect was abolished by CB2 antagonist co-administration and absent in CB2 knockout mice, but not affected by CB1 antagonism. Pharmacological inhibition (WWL70), CB1/CB2 receptor antagonists, CB2 knockout mice, EAE behavioral and histological endpoints Neuropharmacology Medium 26189763
2016 ABHD6 negatively regulates surface delivery and synaptic function of AMPA receptors independent of its hydrolase activity. ABHD6 overexpression reduced GluA1 surface expression and glutamate-induced currents in HEK293T cells expressing GluA1+stargazin; CRISPR/Cas9 knockout or shRNA knockdown in neurons increased AMPAR-mediated transmission. A GFCLIPQ motif in the GluA1 C-terminus is required for this inhibitory effect, and ABHD6 physically binds the C-terminal tail of GluA1. Overexpression and CRISPR/Cas9 KO in neurons, whole-cell patch-clamp electrophysiology, surface biotinylation, co-immunoprecipitation/pulldown, mutagenesis of GluA1 C-terminus Proceedings of the National Academy of Sciences of the United States of America High 27114538
2017 ABHD6 suppresses AMPAR-mediated currents and surface expression of GluA2- and GluA3-containing receptors in HEK293T cells; the C-terminal domains of GluA2 and GluA3 are required for ABHD6 binding and for its inhibitory effects. Pulldown experiments confirmed ABHD6 binds GluA1-3, and deletion of GluA C-terminal domains abolishes this binding. Overexpression in HEK293T cells, whole-cell patch-clamp, surface biotinylation, pulldown assays, C-terminal deletion constructs Frontiers in molecular neuroscience Medium 28303090
2019 Global deletion of ABHD6 increases circulating BMP concentrations in mice, and a human patient with a loss-of-function mutation in ABHD6 shows an altered circulating BMP profile, confirming ABHD6 as a physiologically relevant BMP hydrolase in vivo. ABHD6 global knockout mice, lipidomics of plasma/liver, human patient with ABHD6 loss-of-function mutation Journal of lipid research High 30894461
2020 Adipose-specific ABHD6 deletion increases 2-MAG levels in visceral WAT under cold stress, which activates PPARα in white adipocytes, leading to elevated expression and activity of glycerolipid/free fatty acid (GL/FFA) cycle enzymes and increased cold tolerance without changes in UCP1. Adipose-specific ABHD6 KO mice, cold tolerance assay, lipidomics (nuclear 2-MAG), PPARα target gene expression, GL/FFA cycle enzyme activity assays JCI insight Medium 33201859
2020 ABHD6 functions as the primary MAG lipase in NSCLC and acts as an oncogene; ABHD6 silencing reduced cancer cell migration, invasion, and metastasis in vivo, while overexpression promoted malignancy. ABHD6 blockade induced intracellular MAG accumulation and activated PPARα/γ signaling. siRNA knockdown, ectopic overexpression, xenograft and lung metastasis in vivo models, MAG hydrolase activity assay, PPARα/γ transactivation assay, lipid quantification EBioMedicine Medium 32143183
2020 In response to acute psychosocial stress, the epigenetic corepressor LSD1 directly binds the promoter regulatory regions of Abhd6 and Magl to transcriptionally repress them, thereby increasing 2-AG levels and enhancing ECS-mediated synaptic modulation. This negative transcriptional control is lost during chronic stress. Mouse stress models, gene expression analyses, chromatin immunoprecipitation (ChIP) showing LSD1 binding to Abhd6 and Magl promoters Journal of neurochemistry Medium 32141088
2021 CPT1C physically interacts with ABHD6 (demonstrated by co-immunoprecipitation and FRET) and negatively regulates ABHD6 hydrolase activity, thereby modulating 2-AG signaling through CB1 receptors. CPT1C-KO mouse brains show increased ABHD6 activity. This regulation is dependent on CPT1C's malonyl-CoA sensing: fasting (which reduces brain malonyl-CoA) increases ABHD6 activity in hypothalamus of WT but not CPT1C-KO mice. Co-immunoprecipitation, FRET assay, fluorescent ABHD6 activity assay in cells and brain tissues, CPT1C-KO mice, cAMP assay for CB1 signaling British journal of pharmacology High 33444462
2023 ABHD6 activity controls extrasynaptic (tonic) GABAAR currents in dentate granule cells, but not synaptic (phasic) currents. Heterozygous Abhd6 mutation and pharmacological ABHD6 inhibition reduced thermally induced seizures and premature lethality in Scn1a+/- (Dravet syndrome) mice through GABAAR potentiation. Abhd6+/- genetic mouse model crossed with Scn1a+/-, pharmacological inhibition, brain slice electrophysiology measuring tonic and phasic GABAAR currents Neurobiology of disease High 36990366
2023 ABHD6 is required for neuronal activity-dependent endocytosis of surface AMPARs independent of its hydrolase activity. ABHD6 KO mice show impaired hippocampal LTD and synaptic downscaling, with deficits in reversal learning. ABHD6 KO selectively enhanced AMPAR-mediated basal synaptic responses and surface AMPAR expression. ABHD6 KO mice, electrophysiology (LTD, mEPSC), AMPAR internalization assays, surface biotinylation, behavioral reversal learning Progress in neurobiology High 38159878
2024 Loss of ABHD6 in nucleus accumbens (postsynaptic) neurons, but not in ventral tegmental area (presynaptic) neurons, completely prevents diet-induced obesity in male mice, reduces food- and drug-seeking, and attenuates inhibitory synaptic transmission onto medium spiny neurons. Intraventricular infusion of an ABHD6 inhibitor also restrains appetite and promotes weight loss. Region-specific viral ABHD6 knockdown/knockout (three viral approaches), electrophysiology (inhibitory synaptic transmission), behavioral assays, intraventricular pharmacology Nature communications High 39681558
2025 ABHD6 is identified as a major lysophosphatidylserine (lyso-PS) lipase in the mammalian liver and kidneys (distinct from ABHD12, which controls lyso-PS in the brain). Pharmacological inhibition of ABHD6 validates its lyso-PS lipase activity in vivo, and ABHD6 is functionally designated as the major lyso-PS lipase in primary hepatocytes, mouse liver, and kidneys. In vitro inhibitor screen against membrane fractions of multiple tissues, pharmacological validation in vivo, primary hepatocyte assays The Journal of biological chemistry Medium 39761854
2026 Lactylation of ABHD6 at K245 (driven by Warburg-effect-elevated lactate in lenvatinib-resistant HCC) triggers mitochondrial translocation of ABHD6, where it acts as a scaffold binding FIS1 and displacing DRP1, thereby stabilizing hyperfused mitochondria and conferring drug resistance. This function is independent of catalysis but requires an unoccupied S148 catalytic site; inhibitors that occupy S148 or block lactate production prevent ABHD6-FIS1 complex formation and restore lenvatinib sensitivity. K245 lactylation identification, mitochondrial fractionation, co-immunoprecipitation of ABHD6-FIS1 complex, DRP1 displacement assay, catalytic site mutagenesis, pharmacological occupancy of S148, in vitro and in vivo resistance models Cancer research Medium 41861279
2023 ABHD6 suppression in macrophages under nutrient excess leads to accumulation of 2-MAG species that activate PPAR signaling, promoting anti-inflammatory (M2/MMe) macrophage polarization over pro-inflammatory (M1) polarization. KT203 inhibition or ABHD6-KO in MMe-polarized macrophages attenuated pro-inflammatory cytokines and upregulated lipid metabolism genes via PPARs. ABHD6-KO mice, pharmacological inhibition (KT203), flow cytometry of adipose tissue macrophages, cytokine measurement, lipidomics of cellular and secreted MAG species, PPAR target gene expression Molecular metabolism Medium 37838014
2024 ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner: in the presence of TARP γ-2 (but not alone), ABHD6 accelerates deactivation and desensitization of GluA1 and GluA2(Q)-containing homomeric and GluA1/GluA2(R)/GluA3(R) heteromeric receptors, and slows recovery from desensitization of GluA1 flip isoform. ABHD6-KO neurons displayed slower deactivation and desensitization. Outside-out patch recording with ultra-fast glutamate application in HEK293T cells expressing various AMPAR/TARP/ABHD6 combinations; ABHD6-KO neurons bioRxivpreprint Medium

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors. Nature neuroscience 356 20657592
2011 The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors. Acta physiologica (Oxford, England) 221 21418147
2012 Biochemical and pharmacological characterization of human α/β-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12). Journal of lipid research 150 22969151
2013 Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6. Proceedings of the National Academy of Sciences of the United States of America 132 24101490
2014 ABHD6 blockade exerts antiepileptic activity in PTZ-induced seizures and in spontaneous seizures in R6/2 mice. Neuron 95 25033180
2017 Monoacylglycerol signalling and ABHD6 in health and disease. Diabetes, obesity & metabolism 77 28880480
2013 Discovery and optimization of piperidyl-1,2,3-triazole ureas as potent, selective, and in vivo-active inhibitors of α/β-hydrolase domain containing 6 (ABHD6). Journal of medicinal chemistry 66 24152295
2015 Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis. Neuropharmacology 64 26189763
2016 α/β-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors. Proceedings of the National Academy of Sciences of the United States of America 59 27114538
2019 ABHD6: Its Place in Endocannabinoid Signaling and Beyond. Trends in pharmacological sciences 48 30853109
2015 α/β Hydrolase Domain-containing 6 (ABHD6) Degrades the Late Endosomal/Lysosomal Lipid Bis(monoacylglycero)phosphate. The Journal of biological chemistry 48 26491015
2019 Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans. Journal of lipid research 41 30894461
2008 An unannotated alpha/beta hydrolase superfamily member, ABHD6 differentially expressed among cancer cell lines. Molecular biology reports 36 18360779
2020 Adipose ABHD6 regulates tolerance to cold and thermogenic programs. JCI insight 34 33201859
2018 Deregulation of the endocannabinoid system and therapeutic potential of ABHD6 blockade in the cuprizone model of demyelination. Biochemical pharmacology 34 30075103
2015 Comparative molecular field analysis and molecular dynamics studies of α/β hydrolase domain containing 6 (ABHD6) inhibitors. Journal of molecular modeling 31 26350245
2020 Enhanced monoacylglycerol lipolysis by ABHD6 promotes NSCLC pathogenesis. EBioMedicine 28 32143183
2009 High expression of the evolutionarily conserved alpha/beta hydrolase domain containing 6 (ABHD6) in Ewing tumors. Cancer science 27 19793082
2017 WWL70 attenuates PGE2 production derived from 2-arachidonoylglycerol in microglia by ABHD6-independent mechanism. Journal of neuroinflammation 26 28086912
2014 Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors. ChemMedChem 26 25504894
2014 PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6. Annals of the rheumatic diseases 23 24534757
2021 The endocannabinoid 2-arachidonoylglycerol and dual ABHD6/MAGL enzyme inhibitors display neuroprotective and anti-inflammatory actions in the in vivo retinal model of AMPA excitotoxicity. Neuropharmacology 20 33450278
2020 Termination of acute stress response by the endocannabinoid system is regulated through lysine-specific demethylase 1-mediated transcriptional repression of 2-AG hydrolases ABHD6 and MAGL. Journal of neurochemistry 20 32141088
2023 ABHD6 and MAGL control 2-AG levels in the PAG and allodynia in a CSD-induced periorbital model of headache. Frontiers in pain research (Lausanne, Switzerland) 18 37287623
2018 Structural properties and role of the endocannabinoid lipases ABHD6 and ABHD12 in lipid signalling and disease. Amino acids 18 30564946
2022 Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120/ABHD6. Drug design, development and therapy 17 36238196
2018 Re-examining the potential of targeting ABHD6 in multiple sclerosis: Efficacy of systemic and peripherally restricted inhibitors in experimental autoimmune encephalomyelitis. Neuropharmacology 17 30171986
2017 The Inhibitory Effect of α/β-Hydrolase Domain-Containing 6 (ABHD6) on the Surface Targeting of GluA2- and GluA3-Containing AMPA Receptors. Frontiers in molecular neuroscience 17 28303090
2022 α/β-Hydrolase Domain-Containing 6 (ABHD6)- A Multifunctional Lipid Hydrolase. Metabolites 16 36005632
2020 Impact of tetrahydrocannabinol on the endocannabinoid 2-arachidonoylglycerol metabolism: ABHD6 and ABHD12 as novel players in human placenta. Biochimica et biophysica acta. Molecular and cell biology of lipids 16 32829065
2021 Carnitine palmitoyltransferase 1C negatively regulates the endocannabinoid hydrolase ABHD6 in mice, depending on nutritional status. British journal of pharmacology 13 33444462
2020 Therapeutic potential of targeting α/β-Hydrolase domain-containing 6 (ABHD6). European journal of medicinal chemistry 10 32371333
2019 Pseudomonas aeruginosa esterase PA2949, a bacterial homolog of the human membrane esterase ABHD6: expression, purification and crystallization. Acta crystallographica. Section F, Structural biology communications 10 30950828
2012 Highly predictive ligand-based pharmacophore and homology models of ABHD6. Chemical biology & drug design 10 23110439
2024 Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying Circ-Tulp4 Attenuate Diabetes Mellitus with Nonalcoholic Fatty Liver Disease by Inhibiting Cell Pyroptosis through the HNRNPC/ABHD6 Axis. Tissue engineering and regenerative medicine 9 39546192
2017 Chiral disubstituted piperidinyl ureas: a class of dual diacylglycerol lipase-α and ABHD6 inhibitors. MedChemComm 8 30108813
2025 Identification of ABHD6 as a lysophosphatidylserine lipase in the mammalian liver and kidneys. The Journal of biological chemistry 7 39761854
2023 ABHD6 suppression promotes anti-inflammatory polarization of adipose tissue macrophages via 2-monoacylglycerol/PPAR signaling in obese mice. Molecular metabolism 7 37838014
2015 Revisiting 1,3,4-Oxadiazol-2-ones: Utilization in the Development of ABHD6 Inhibitors. Bioorganic & medicinal chemistry 7 26344596
2024 ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice. Nature communications 6 39681558
2025 Inhibition of endocannabinoid hydrolases MAGL, FAAH and ABHD6 by AKU-005 reduces ex vivo cortical spreading depression. The journal of headache and pain 5 40269679
2023 ABHD6 drives endocytosis of AMPA receptors to regulate synaptic plasticity and learning flexibility. Progress in neurobiology 5 38159878
2016 A Sensitive and Versatile Fluorescent Activity Assay for ABHD6. Methods in molecular biology (Clifton, N.J.) 5 27245903
2025 Suppression of adipocyte ABHD6 favors anti-inflammatory and adipogenic programs to preserve adipose tissue fitness in obesity. Molecular metabolism 4 40886915
2023 The serine hydrolase ABHD6 controls survival and thermally induced seizures in a mouse model of Dravet syndrome. Neurobiology of disease 3 36990366
2022 Utilizing PET and MALDI Imaging for Discovery of a Targeted Probe for Brain Endocannabinoid α/β-Hydrolase Domain 6 (ABHD6). Journal of medicinal chemistry 3 36516997
2024 ABHD6 suppresses colorectal cancer progression via AKT signaling pathway. Molecular carcinogenesis 2 38197491
2025 ABHD6 suppression attenuates pro-inflammatory responses in mice and promotes anti-inflammatory polarization of macrophages during endotoxin stress. Biochimica et biophysica acta. Molecular and cell biology of lipids 1 41061850
2021 ABHD6 Inhibition Rescues a Sex-Dependent Deficit in Motor Coordination in The HdhQ200/200 Mouse Model of Huntington's Disease. Journal of neurology and neurological disorders 1 37720694
2026 Lactylation Converts ABHD6 into a Mitochondrial Regulator that Drives Lenvatinib Resistance in Hepatocellular Carcinoma. Cancer research 0 41861279
2025 The Lipid Hydrolase ABHD6 is a Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Related Hepatocellular Carcinoma. bioRxiv : the preprint server for biology 0 40766524

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