Affinage

GFRAL

GDNF family receptor alpha-like · UniProt Q6UXV0

Length
394 aa
Mass
44.5 kDa
Annotated
2026-06-10
48 papers in source corpus 23 papers cited in narrative 25 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

GFRAL is the high-affinity receptor for GDF15 and the molecular gateway through which this cytokine controls feeding, energy balance, and aversive physiology (PMID:28846097, PMID:28846098, PMID:28846099). Ligand binding occurs through the GFRAL extracellular domain, which engages the C-terminus of GDF15 (PMID:37495041), but GFRAL itself has no intrinsic signaling capacity: productive responses require GDF15-driven recruitment of the coreceptor RET to GFRAL, which then activates ERK and AKT signaling (PMID:28846097, PMID:28846098, PMID:28846099, PMID:32661391). Expression of GFRAL is overwhelmingly restricted to neurons of the brainstem area postrema and nucleus of the solitary tract, with no reliable detection in peripheral tissues across multiple species and orthogonal methods (PMID:28846097, PMID:28846098, PMID:28846099, PMID:39608751); regional knockdown in the AP/NTS recapitulates and worsens diet-induced obesity, establishing this circuit as the principal site of GDF15 action (PMID:31152154, PMID:28846097). Activated GFRAL neurons project most strongly to CGRP-expressing parabrachial neurons to drive conditioned taste aversion and anorexia, and act through BDNF-expressing mNTS neurons to reduce food intake and promote fatty acid oxidation (PMID:33593916, PMID:39737892). Beyond central anorexia, the GFRAL-RET axis engages a peripheral sympathetic-lipolytic program in adipose tissue that contributes to weight loss independently of feeding (PMID:32661391), modulates glucose homeostasis and insulin sensitivity via area postrema neurons (including effects required for metformin action) (PMID:38064571), and broadly regulates systemic energy metabolism, body temperature, and aversive/anxiety-like states (PMID:38507407, PMID:36271504). GFRAL signaling is negatively regulated by membrane-bound MT1-MMP (MMP14), which proteolytically inactivates GFRAL in GFRAL+ neurons during overnutrition, dampening GDF15 responsiveness in obesity (PMID:35177851). The pathway mediates pathological states including chemotherapy-induced fatigue (PMID:36427806), and GFRAL is an actively pursued therapeutic target, with antagonist antibodies, peptides, and bicyclic mimetics that block GDF15-driven RET recruitment (PMID:32661391, PMID:37506293, PMID:41066664).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2017 High

    Establishing the orphan receptor for the metabolic cytokine GDF15 was the central question; identifying GFRAL as the high-affinity GDF15 receptor that is genetically required for GDF15-induced anorexia defined the entire axis.

    Evidence Radioligand binding, GFRAL knockout mice, and recombinant GDF15 administration, replicated across three groups

    PMID:28846097 PMID:28846098 PMID:28846099

    Open questions at the time
    • Did not resolve the structural basis of binding
    • Intracellular signaling mechanism not yet defined at this stage
  2. 2017 High

    Because GFRAL lacks an obvious signaling module, how it transmits a signal was unknown; demonstrating an obligatory requirement for the coreceptor RET established the two-component receptor architecture.

    Evidence Cell-based signaling assays with loss-of-function and reconstitution

    PMID:28846097 PMID:28846098 PMID:28846099

    Open questions at the time
    • Stoichiometry and assembly order of the GFRAL-RET complex not defined
    • Downstream effectors only partially mapped
  3. 2017 High

    Where GDF15 acts was unresolved; restricting GFRAL expression to brainstem AP/NTS neurons across species localized the entire GDF15 metabolic effect to a central circuit.

    Evidence In situ hybridization and expression profiling across mouse, rat, monkey, and human

    PMID:28846097 PMID:28846098 PMID:28846099

    Open questions at the time
    • Did not map downstream neural projections
    • Did not exclude low-level expression detectable only by more sensitive methods
  4. 2017 High

    Whether GFRAL had a homeostatic role beyond pharmacological GDF15 was unknown; KO mice on high-fat diet showed exacerbated obesity and insulin resistance, defining an endogenous metabolic function.

    Evidence Gfral knockout mice with high-fat diet challenge and metabolic phenotyping

    PMID:28846097

    Open questions at the time
    • Did not establish the endogenous GDF15 source driving this tone
    • Circuit-level basis not addressed
  5. 2019 Medium

    To confirm AP/NTS as the operative CNS site rather than an expression correlate, regional knockdown was required; localized AAV-shRNA in AP/NTS produced dose-dependent weight gain.

    Evidence AAV-shRNA regional knockdown with quantitative IHC and metabolic phenotyping

    PMID:31152154

    Open questions at the time
    • Single lab
    • Downstream circuit not addressed
  6. 2020 High

    Whether GDF15-induced weight loss was purely anorexic was unresolved; an antagonist antibody plus sympathectomy and ATGL-KO revealed a peripheral sympathetic-lipolytic axis acting independently of food intake.

    Evidence Antagonistic mAb 3P10, chemical sympathectomy, ATGL knockout, and adipose transcriptomics

    PMID:32661391

    Open questions at the time
    • Neural relay from GFRAL neurons to sympathetic output not delineated
    • Relative contribution of lipolysis vs anorexia to total weight loss not quantified
  7. 2021 High

    The downstream circuit for aversion and anorexia was unknown; chemogenetic and epistasis experiments placed GFRAL neurons upstream of CGRP parabrachial neurons in an aversive pathway.

    Evidence DREADD activation of GFRAL neurons, conditional Gfral mice, TRAP-seq, CTA, and CGRP-PBN silencing

    PMID:33593916

    Open questions at the time
    • Neurotransmitter identity of GFRAL neuron output not defined
    • Did not address parallel non-aversive branches
  8. 2022 High

    How GFRAL responsiveness is downregulated in obesity was unknown; identifying MT1-MMP as a proteolytic inactivator of GFRAL revealed a negative-regulatory mechanism that blunts GDF15 signaling during overnutrition.

    Evidence GFRAL+ neuron-specific MT1-MMP conditional KO, proteolytic cleavage assay, and GFRAL-KO epistasis

    PMID:35177851

    Open questions at the time
    • Cleavage site and fragment fate not defined
    • Trigger linking overnutrition to MT1-MMP activation not resolved
  9. 2022 Medium

    Whether GFRAL mediates pathological wasting and behavior beyond diet was open; muscle-mitochondrial-dysfunction and chemotherapy models showed GFRAL drives anorexia, CRH induction, anxiety-like behavior, and fatigue.

    Evidence GFRAL KO crosses, behavioral assays, hypothalamic gene expression, and anti-GFRAL neutralizing antibody with wheel-running

    PMID:36271504 PMID:36427806

    Open questions at the time
    • Circuit basis of CRH induction and fatigue not mapped
    • Single lab per phenotype
  10. 2023 Medium

    The ligand-receptor binding interface and tractability for antagonism were undefined; peptide mapping localized binding to the GDF15 C-terminus/GFRAL extracellular domain and yielded functional antagonists.

    Evidence SPOT/peptide arrays, SPR, flow cytometry, and in vivo rat anorexia models for GRASP and C-terminal fragments

    PMID:37495041 PMID:37506293

    Open questions at the time
    • High-resolution structure of the complex not solved here
    • Potency in the micromolar range for some agents
  11. 2024 Medium

    Whether GDF15-GFRAL controls glucose homeostasis independently of weight was unresolved; AP infusion and regional knockdown showed GFRAL is required for GDF15- and metformin-driven glucose tolerance improvements.

    Evidence Intracranial GDF15 infusion, AP-specific GFRAL knockdown, and hyperinsulinemic-euglycemic clamp in rats

    PMID:38064571

    Open questions at the time
    • Efferent pathway controlling hepatic glucose production not defined
    • Single lab
  12. 2024 Medium

    The breadth of physiology controlled by GFRAL neurons and their downstream relay were incompletely defined; activation studies and BDNF-mNTS epistasis revealed thermoregulatory/torpor effects and a required BDNF-mNTS node.

    Evidence Chemogenetic/optogenetic activation of GFRAL+ neurons with metabolomics; genetic ablation and activation of BDNF-mNTS neurons

    PMID:38507407 PMID:39737892

    Open questions at the time
    • Integration of CGRP-PBN and BDNF-mNTS branches not reconciled
    • Single lab per study
  13. 2024 High

    Whether reported peripheral GFRAL expression is real was contested; three orthogonal detection methods confirmed expression is overwhelmingly restricted to brainstem AP/NTS and not peripheral tissues.

    Evidence Gfral:eGFP reporter mice, smFISH, and scRNA-seq across mouse and human tissues

    PMID:39608751

    Open questions at the time
    • Cannot fully exclude rare or transient peripheral expression below detection
    • Does not adjudicate every individual peripheral claim
  14. 2025 Medium

    Whether the central GFRAL axis intersects systemic immunity and disease was unknown; brainstem GFRAL activation was shown to suppress autoimmune T cell responses via splenic β-adrenergic signaling, and regional knockdown improved ALS outcomes.

    Evidence GDF15 KO, chemogenetic GFRAL+ activation, norepinephrine/integrin analysis in MS models; AP/NTS shRNA knockdown with microglial depletion in hSOD1G93A mice

    PMID:39672239 PMID:41540266

    Open questions at the time
    • Efferent neuroimmune relay incompletely defined
    • Single lab per disease model
  15. 2025 Medium

    Therapeutic blockade of the GDF15-GFRAL interface remained to be optimized; structure-guided bicyclic peptide tandems mimicking dimeric GDF15 bound GFRAL at picomolar affinity and blocked RET recruitment.

    Evidence Phage display, structure-guided design, affinity measurement, and functional cell signaling assay

    PMID:41066664

    Open questions at the time
    • In vivo efficacy not established in this study
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the GFRAL-RET complex is assembled at atomic resolution and how its divergent outputs (CGRP-PBN aversion, BDNF-mNTS anorexia, sympathetic lipolysis, glucose control, neuroimmune signaling) are routed through distinct GFRAL neuron subpopulations remain unresolved.
  • No high-resolution structure of the ternary GDF15-GFRAL-RET complex
  • Molecular logic dividing aversive vs metabolic vs immune branches unknown
  • Identity and connectivity of GFRAL neuron subtypes not fully resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 3 GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2
Partners
GDF15MMP14RET
Complex memberships
GFRAL-RET coreceptor complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 GFRAL is the high-affinity receptor for GDF15; GDF15 binds GFRAL and genetic deletion of GFRAL abrogates GDF15-induced decreases in food intake and body weight in mice, establishing GFRAL as the bona fide receptor mediating metabolic effects of GDF15. Radioligand binding assay, GFRAL knockout mice, recombinant GDF15 administration Nature medicine High 28846097 28846098 28846099
2017 GFRAL requires association with the coreceptor RET to elicit intracellular signaling in response to GDF15 stimulation; GDF15-induced cell signaling requires the GFRAL-RET interaction. Cell-based signaling assays, co-receptor requirement demonstrated by loss-of-function and reconstitution experiments Nature medicine High 28846097 28846098 28846099
2017 Gfral mRNA is expressed specifically in neurons of the area postrema and nucleus of the solitary tract in the hindbrain (mouse, rat, monkey, human), and not in peripheral tissues, indicating GDF15-GFRAL regulation of food intake operates via a central mechanism. In situ hybridization, mRNA expression profiling, immunohistochemistry across species Nature medicine High 28846097 28846098 28846099
2017 Diet-induced obesity and insulin resistance are exacerbated in GFRAL-deficient mice, indicating a homeostatic role for GFRAL in metabolism. Gfral knockout mouse model, high-fat diet challenge, metabolic phenotyping Nature medicine High 28846097
2005 GFRAL (GRAL-A) protein localizes predominantly to the plasma membrane; overexpression of GFRAL-A protected PC12 cells and cultured hippocampal neurons from serum starvation-induced apoptosis, associated with inhibition of the JNK signaling pathway. Subcellular fractionation/immunofluorescence for localization; cell viability assays and JNK pathway analysis for neuroprotective function Journal of neurochemistry Medium 16086688
2005 GFRAL (GRAL) has two splice variants: full-length GRAL-A (2080 bp mRNA) and short GRAL-B (1833 bp mRNA), with primary CNS expression in adult mouse; GRAL-A shares ~30% amino acid identity with GFRα-3. cDNA cloning, sequence analysis, Northern blot/RT-PCR expression profiling Journal of neurochemistry Medium 16086688
2020 Antagonistic monoclonal antibody 3P10 targeting GFRAL inhibits RET signaling by preventing the GDF15-driven interaction of RET with GFRAL on the cell surface; activation of the GFRAL-RET pathway induces expression of lipid metabolism genes in adipose tissue; peripheral chemical sympathectomy and loss of adipose triglyceride lipase protect mice from GDF15-induced weight loss, revealing a peripheral sympathetic axis by which GDF15 elicits lipolytic responses independently of anorexia. Antagonistic monoclonal antibody, RET signaling assays, sympathectomy, ATGL knockout mice, gene expression profiling in adipose tissue Nature medicine High 32661391
2021 Artificial activation of GFRAL-expressing neurons inhibited feeding, decreased gastric emptying, and promoted conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus targeting CGRP-expressing neurons, and silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15, placing GFRAL neurons upstream of CGRPPBN in an aversive pathway. Chemogenetic activation (DREADD) of GFRAL neurons, conditional Gfral mice, TRAP-seq, CTA assay, CGRPPBN neuron silencing Proceedings of the National Academy of Sciences of the United States of America High 33593916
2019 Localized AAV-shRNA knockdown of GFRAL in the area postrema and nucleus of the solitary tract of mice commencing high-fat diet caused increased body weight and adiposity proportional to the degree of GFRAL knockdown, confirming AP/NTS as the major CNS site of GDF15 action. AAV-shRNA regional knockdown, quantitative immunohistochemistry, metabolic phenotyping International journal of obesity (2005) Medium 31152154
2022 Membrane-bound MT1-MMP (MMP14) proteolytically inactivates GFRAL in GFRAL+ neurons; overnutrition-induced obesity increased MT1-MMP activation which suppressed GDF15-GFRAL signaling. Genetic ablation of MT1-MMP specifically in GFRAL+ neurons restored GFRAL expression and reduced weight gain. Depletion of GFRAL abolished the anti-obesity effects of MT1-MMP inhibition. Cell-specific conditional KO (MT1-MMP in GFRAL+ neurons), proteolytic cleavage assay, GFRAL KO epistasis, in vivo obesity models Nature metabolism High 35177851
2024 Direct acute infusion of GDF15 into the area postrema increased intravenous glucose tolerance and insulin sensitivity and lowered hepatic glucose production independently of food intake, weight, and plasma insulin; knockdown of GFRAL in the area postrema negated these effects and also negated metformin-induced glucose tolerance improvement. Intracranial infusion, GFRAL knockdown in area postrema, hyperinsulinemic-euglycemic clamp, conscious unrestrained rat model Diabetes Medium 38064571
2024 Cell-specific acute activation of GFRAL+ neurons caused hypothermia, torpor-like state, release of stress hormones, shift from glucose to lipid oxidation, impaired insulin sensitivity and glucose tolerance, decreased skeletal muscle glucose uptake, but augmented visceral fat glucose uptake. Chemogenetic and optogenetic activation of GFRAL+ neurons, metabolomics, transcriptomics, glucose uptake assays Cell reports Medium 38507407
2022 In a mouse model of muscle-specific mitochondrial dysfunction, GFRAL is required for systemic energy metabolism via daytime-restricted anorexia; GFRAL signaling mediates hypothalamic corticotropin-releasing hormone induction (without elevated corticosterone) and governs anxiety-like behavior. GFRAL KO crossed with muscle mitochondrial dysfunction mouse model, behavioral assays, hypothalamic gene expression analysis Life science alliance Medium 36271504
2022 A neutralizing monoclonal antibody to GFRAL prevented cisplatin-induced decrease in wheel running (fatigue behavior) in mice, demonstrating that the GDF15/GFRAL axis mediates chemotherapy-induced fatigue. Anti-GFRAL neutralizing antibody, voluntary wheel running assay, mGDF15-Fc administration Brain, behavior, and immunity Medium 36427806
2020 In endothelial cells, MIC-1/GDF15 promotes angiogenesis via MEK/ERK- and PI3K/Akt-dependent pathways; siRNA knockdown of GFRAL abrogated these MIC-1 signaling events, identifying GFRAL as an endothelial cell receptor for MIC-1. siRNA knockdown of GFRAL in endothelial cells, angiogenesis assays, signaling pathway analysis (MEK/ERK, PI3K/Akt) Journal of cellular physiology Medium 33151561
2020 In pancreatic ductal adenocarcinoma cells, GFRAL mediates GDF-15-induced tumor cell proliferation and metastasis; overexpression of GFRAL in pancreatic cancer cells enhanced GDF-15 biological effects. GFRAL overexpression, GDF-15 knockdown, xenotransplantation in nude mice, in vitro proliferation assays Aging Low 33201838
2023 GDF-15 inhibits ADP-induced human platelet aggregation through binding to GFRAL on platelets and signaling via the GFRAL/RET complex, inhibiting AKT and ERK activation; immunoprecipitation confirmed GFRAL as the binding partner of GDF-15 on platelets. Platelet aggregation assay, receptor microarray, immunoprecipitation, ERK/AKT pathway analysis, RET agonist/inhibitor experiments Biomolecules Low 38254638
2023 A peptide antagonist of GFRAL (GRASP) developed by library screening binds GFRAL (confirmed by surface plasmon resonance and flow cytometry) and blocks GDF15-mediated RET recruitment; in vivo GRASP attenuated GDF15-induced nausea and anorexia in rats. Peptide library screen, surface plasmon resonance, flow cytometry, in vivo rat anorexia model Journal of medicinal chemistry Medium 37506293
2023 GDF15 C-terminal peptide fragments bind the extracellular domain of GFRAL (SPOT arrays) and inhibit GFRAL activity in cells expressing the GFRAL/RET receptor complex in the micromolar range, identifying the C-terminus of GDF15 as the GFRAL-binding region. SPOT peptide arrays, solid-phase peptide synthesis, functional cell assays with GFRAL/RET-expressing cells Peptides Medium 37495041
2024 BDNFmNTS neurons in the medial nucleus of the tractus solitarius are required downstream of GFRAL/GLP1R neurons for weight-reducing actions of GDF15; acute activation of BDNFmNTS neurons is sufficient to reduce food intake and drive fatty acid oxidation. Genetic ablation of BDNFmNTS neurons, chemogenetic activation, GDF15 and Exendin-4 treatment, metabolic phenotyping Nature communications Medium 39737892
2026 GDF15 suppresses autoimmune T cell responses through GFRAL activation on brainstem neurons, leading to β-adrenergic signaling and norepinephrine synthesis in the spleen, which decreases integrin expression on T cells required for blood-brain barrier transmigration; chemogenetic activation of GFRAL+ neurons recapitulated these neuroimmune effects. GDF15 KO mice, recombinant GDF15, neuronal gene delivery, chemogenetic activation of GFRAL+ neurons, norepinephrine measurement, integrin expression analysis, preclinical MS models Nature immunology Medium 41540266
2025 Bicyclic peptide tandems mimicking homodimeric GDF15 bind GFRAL with picomolar affinity and inhibit GDF15-GFRAL protein-protein interaction to prevent RET-induced intracellular signaling, as confirmed in a functional cell signaling assay; structural data guided conversion of monomeric hits to tandem molecules. Phage display, structure-guided design, binding affinity measurement, functional cell signaling assay, pharmacokinetic analysis Journal of medicinal chemistry Medium 41066664
2024 GFRAL expression, assessed using Gfral:eGFP reporter mice, single-molecule FISH, and scRNA-seq, is overwhelmingly restricted to the brainstem AP/NTS; Gfral-labelled cells were not reliably detected in other brain regions or peripheral tissues using three independent detection methods. Gfral:eGFP reporter mice, single-molecule fluorescence in situ hybridization (smFISH), scRNA-seq of human tissues Molecular metabolism High 39608751
2025 In melanoma cells, CAF-derived GDF15 binds GFRAL, promoting RET phosphorylation and downstream signaling that increases tumor cell stemness and secretion of CCL18 and TGF-β, inducing macrophage M2 polarization; confirmed by co-immunoprecipitation. Co-immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assay, lentiviral transfection, flow cytometry, recombinant protein rescue, Cre-loxP KO mice Journal for immunotherapy of cancer Low 40555562
2024 GFRAL silencing by shRNA in the area postrema/NTS of ALS model mice (hSOD1G93A) induced weight gain, reduced adipose tissue wasting, ameliorated motor function and muscle atrophy, and prolonged survival; microglial depletion reduced brainstem GDF15 expression and lipolytic gene expression in adipose tissue, suggesting microglial involvement in mediating GFRAL-dependent effects. shRNA regional knockdown, PLX5622 microglial depletion, body weight and motor function assays, lipolytic gene expression analysis Brain, behavior, and immunity Medium 39672239

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nature medicine 626 28846097
2017 The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nature medicine 552 28846098
2017 GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nature medicine 543 28846099
2018 The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases. Cell metabolism 336 30184485
2020 Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice. Nature medicine 258 32661391
2020 The GDF15-GFRAL Pathway in Health and Metabolic Disease: Friend or Foe? Annual review of physiology 179 33228454
2020 Insights Into Mechanisms of GDF15 and Receptor GFRAL: Therapeutic Targets. Trends in endocrinology and metabolism: TEM 136 33172749
2018 Uniting GDF15 and GFRAL: Therapeutic Opportunities in Obesity and Beyond. Trends in endocrinology and metabolism: TEM 102 29866502
2021 GFRAL-expressing neurons suppress food intake via aversive pathways. Proceedings of the National Academy of Sciences of the United States of America 78 33593916
2017 Targeting Obesity and Cachexia: Identification of the GFRAL Receptor-MIC-1/GDF15 Pathway. Trends in molecular medicine 67 29129392
2021 GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer. Journal of Cancer 61 33442410
2019 GDF15 mediates adiposity resistance through actions on GFRAL neurons in the hindbrain AP/NTS. International journal of obesity (2005) 57 31152154
2005 Identification, expression and functional characterization of the GRAL gene. Journal of neurochemistry 57 16086688
2022 The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. Cell reports 37 36001956
2024 GFRAL Is Widely Distributed in the Brain and Peripheral Tissues of Mice. Nutrients 33 38474863
2020 Upregulated GDF-15 expression facilitates pancreatic ductal adenocarcinoma progression through orphan receptor GFRAL. Aging 33 33201838
2022 Body weight regulation via MT1-MMP-mediated cleavage of GFRAL. Nature metabolism 31 35177851
2024 Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis. Nature communications 30 38310105
2024 Activation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor. Cell reports 26 38507407
2022 The GDF15-GFRAL axis mediates chemotherapy-induced fatigue in mice. Brain, behavior, and immunity 24 36427806
2023 Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice. Molecular metabolism 22 37356805
2025 Ectopic expression of GDF15 in cancer-associated fibroblasts enhances melanoma immunosuppression via the GFRAL/RET cascade. Journal for immunotherapy of cancer 21 40555562
2024 Fatty Acids Increase GDF15 and Reduce Food Intake Through a GFRAL Signaling Axis. Diabetes 20 37847913
2021 Expression of the Body-Weight Signaling Players: GDF15, GFRAL and RET and their clinical relevance in Gastric Cancer. Journal of Cancer 20 34149933
2009 Imprecise transcription termination within Escherichia coli greA leader gives rise to an array of short transcripts, GraL. Nucleic acids research 16 20008510
2022 Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior. Life science alliance 15 36271504
2024 GDNF family receptor alpha-like (GFRAL) expression is restricted to the caudal brainstem. Molecular metabolism 14 39608751
2024 Acute Activation of GFRAL in the Area Postrema Contributes to Glucose Regulation Independent of Weight. Diabetes 12 38064571
2020 Macrophage inhibitory cytokine-1 promotes angiogenesis by eliciting the GFRAL-mediated endothelial cell signaling. Journal of cellular physiology 11 33151561
2024 Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling. Nature communications 10 39737892
2023 GDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex. Biomolecules 10 38254638
2023 Creation of a Peptide Antagonist of the GFRAL-RET Receptor Complex for the Treatment of GDF15-Induced Malaise. Journal of medicinal chemistry 9 37506293
2017 Targeting both sides of the GDF15-GFRAL-RET receptor complex: A new approach to achieve body weight homeostasis. Genes & diseases 9 30258922
2025 GDF15 Analogues Acting as GFRAL Ligands. ChemMedChem 8 39907315
2023 Identification of GDF15 peptide fragments inhibiting GFRAL receptor signaling. Peptides 6 37495041
2021 Genome-wide association and transcriptome analysis suggests total serum ghrelin to be linked with GFRAL. European journal of endocrinology 5 33852427
2024 GDF15-GFRAL signaling drives weight loss and lipid metabolism in mouse model of amyotrophic lateral sclerosis. Brain, behavior, and immunity 4 39672239
2023 Neither GLP-1 receptors nor GFRAL neurons are required for aversive or anorectic response to DON (vomitoxin). American journal of physiology. Regulatory, integrative and comparative physiology 4 36912475
2025 Deletion of GFRAL blunts weight lowering effects of FGF21 in female mice. The Journal of endocrinology 3 40167255
2018 A search for the in trans role of GraL, an Escherichia coli small RNA. Acta biochimica Polonica 3 29529101
2026 A GDF-15-GFRAL axis controls autoimmune T cell responses during neuroinflammation. Nature immunology 2 41540266
2025 GFRAL-Fc disarms GDF15 to reprogram tumor immunity and amplify PD-1 efficacy in hepatocellular carcinoma. Cell communication and signaling : CCS 2 41094454
2025 Design of Bicyclic Peptide Tandems Mimicking the Homodimeric GDF15 Protein to Inhibit GDF15-GFRaL-RET Complex Cell Signaling. Journal of medicinal chemistry 1 41066664
2019 Autoregulation of greA Expression Relies on GraL Rather than on greA Promoter Region. International journal of molecular sciences 1 31652493
2026 Association between elevated expression of GDF15/GFRAL and sarcopenia risk. iScience 0 41797911
2026 A loss-of-function variant in GFRAL associates with increased alcohol consumption in humans. bioRxiv : the preprint server for biology 0 41959486
2026 GFRAL is required to mediate changes in systemic metabolism in response to mitochondrial stress in brown adipose tissue. Journal of molecular medicine (Berlin, Germany) 0 41974995
2025 Inhibition of GDF15/GFRAL: A novel opportunity for the treatment of solid tumors. International immunopharmacology 0 41455368

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