Affinage

GFRAL

GDNF family receptor alpha-like · UniProt Q6UXV0

Length
394 aa
Mass
44.5 kDa
Annotated
2026-04-28
48 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GFRAL is the obligate high-affinity receptor for the stress-responsive cytokine GDF15, functioning as a hindbrain-restricted signaling hub that transduces metabolic, behavioral, and neuroimmune signals through recruitment of the co-receptor RET (PMID:28846097, PMID:28846098, PMID:28846099). Expressed predominantly on area postrema and nucleus of the solitary tract neurons, GFRAL–RET activation suppresses food intake via projections to CGRP-expressing parabrachial nucleus neurons and downstream BDNF-mNTS neurons, while simultaneously regulating hepatic glucose production, peripheral sympathetic lipolysis, thermoregulation, and autoimmune T cell responses through β-adrenergic splenic signaling (PMID:33593916, PMID:32661391, PMID:38064571, PMID:38507407, PMID:39737892, PMID:41540266). GFRAL surface availability is negatively regulated by MT1-MMP–mediated proteolytic cleavage, which is upregulated during obesity and limits GDF15 sensitivity; genetic ablation of MT1-MMP in GFRAL-positive neurons restores receptor expression and attenuates weight gain (PMID:35177851). GFRAL signaling also mediates chemotherapy-induced fatigue, mitochondrial stress-driven anorexia and anxiety, and cachexia-associated wasting in neurodegenerative disease models (PMID:36427806, PMID:36271504, PMID:39672239).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2005 Medium

    Before GDF15 was identified as its ligand, GFRAL (then called GRAL) was shown to localize to the plasma membrane and to exert a neuroprotective anti-apoptotic effect by inhibiting JNK signaling, establishing it as a neuronal surface receptor with survival functions.

    Evidence Overexpression in PC12 cells and hippocampal neurons with subcellular fractionation and JNK pathway analysis

    PMID:16086688

    Open questions at the time
    • Overexpression system without identified ligand limits physiological interpretation
    • JNK inhibition mechanism not connected to any upstream signal
    • No in vivo confirmation of neuroprotective role
  2. 2017 High

    The central breakthrough came when four independent groups simultaneously identified GFRAL as the high-affinity receptor for GDF15, demonstrated that GFRAL obligatorily recruits co-receptor RET for signal transduction, and showed that GFRAL expression is restricted to area postrema/NTS neurons — resolving the long-standing mystery of how circulating GDF15 suppresses food intake and body weight.

    Evidence Radioligand binding, Gfral knockout mice, cell-based co-receptor signaling assays, in situ hybridization across species

    PMID:28846097 PMID:28846098 PMID:28846099

    Open questions at the time
    • Downstream intracellular signaling cascades beyond RET phosphorylation were not fully mapped
    • Whether GFRAL functions outside the CNS was not addressed
    • Crystal structure of the ternary GDF15–GFRAL–RET complex not yet determined
  3. 2019 High

    Regional shRNA knockdown quantitatively demonstrated that GFRAL in AP/NTS neurons is both necessary and sufficient for resistance to diet-induced obesity, with adiposity proportional to knockdown efficiency, confirming the anatomical site of action.

    Evidence AAV-shRNA knockdown in AP/NTS with quantitative immunostaining and metabolic phenotyping

    PMID:31152154

    Open questions at the time
    • Neuronal subtypes within AP/NTS expressing GFRAL were not resolved
    • Downstream circuit targets of GFRAL neurons remained uncharacterized
  4. 2020 High

    Antagonistic anti-GFRAL antibody blockade and genetic/pharmacological ablation of peripheral sympathetic nerves revealed that GFRAL–RET signaling drives weight loss partly through a peripheral sympathetic-lipolytic axis involving adipose triglyceride lipase, extending the pathway beyond central anorexia to peripheral lipid mobilization.

    Evidence Anti-GFRAL monoclonal antibody, chemical sympathectomy, ATGL knockout mice, adipose gene expression profiling

    PMID:32661391

    Open questions at the time
    • Neural pathway from brainstem GFRAL neurons to sympathetic outflow not anatomically traced
    • Relative contributions of anorexia versus lipolysis to total weight loss not dissected
  5. 2020 Medium

    GFRAL was detected on endothelial cells where it mediates GDF15-induced proangiogenic signaling via MEK/ERK and PI3K/Akt, suggesting GFRAL function beyond the CNS.

    Evidence siRNA knockdown in endothelial cells with tube formation and sprouting assays

    PMID:33151561

    Open questions at the time
    • Endothelial GFRAL expression not confirmed at protein level in vivo
    • Whether RET is the co-receptor in this context was not tested
    • Single-lab finding not independently replicated
  6. 2021 High

    Circuit-level dissection using Gfral-Cre mice revealed that GFRAL neurons project predominantly to CGRP-expressing parabrachial nucleus neurons, and silencing these downstream neurons abolished GDF15-induced aversion and anorexia, establishing the first defined neural circuit for GDF15 action.

    Evidence Chemogenetic/optogenetic activation of Gfral-Cre neurons, TRAP-Seq, conditional CGRP-PBN silencing, conditioned taste aversion assays

    PMID:33593916

    Open questions at the time
    • Other downstream targets of GFRAL neurons beyond PBN were not explored
    • Whether metabolic effects (glucose, lipid) require CGRP-PBN neurons was not tested
  7. 2022 High

    MT1-MMP was identified as an endogenous negative regulator that proteolytically cleaves GFRAL on neuronal surfaces, with obesity-driven MT1-MMP upregulation explaining reduced GDF15 sensitivity; cell-type-specific MT1-MMP deletion restored GFRAL and protected against weight gain.

    Evidence Proteolytic cleavage assays, conditional MT1-MMP knockout in GFRAL+ neurons, metabolic phenotyping

    PMID:35177851

    Open questions at the time
    • Exact cleavage site on GFRAL not mapped
    • Whether shed GFRAL ectodomain acts as a decoy receptor is unknown
    • Signals upstream of MT1-MMP activation in obesity not identified
  8. 2022 Medium

    Beyond food intake, GFRAL was shown to mediate chemotherapy-induced behavioral fatigue and mitochondrial stress-induced anorexia with anxiety, broadening its role to sickness behavior and stress-associated affective changes.

    Evidence Anti-GFRAL antibody in cisplatin-treated mice (wheel running); Gfral KO crossed with muscle mitochondrial dysfunction model (anxiety assays, CRH expression)

    PMID:36271504 PMID:36427806

    Open questions at the time
    • Specific neuronal populations mediating fatigue versus anorexia versus anxiety not dissected
    • CRH induction pathway downstream of GFRAL not fully characterized
  9. 2023 Medium

    Biochemical and pharmacological dissection of the GDF15–GFRAL binding interface via peptide arrays and designed antagonists (including the GRASP peptide) defined the extracellular interaction surface and provided proof-of-concept that GFRAL blockade attenuates GDF15-induced nausea in vivo.

    Evidence SPOT peptide arrays, surface plasmon resonance, peptide antagonist in rat cisplatin nausea model, GFRAL on platelets by immunoprecipitation and receptor microarray

    PMID:37495041 PMID:37506293 PMID:38254638

    Open questions at the time
    • High-resolution co-crystal structure of antagonist–GFRAL complex not available
    • Platelet GFRAL function in vivo physiological hemostasis not confirmed
    • Selectivity of peptide antagonists over related GDNF-family receptors not fully addressed
  10. 2024 High

    Direct infusion of GDF15 into the area postrema demonstrated that GFRAL activation acutely lowers hepatic glucose production and increases insulin sensitivity independent of food intake or weight change, establishing a food-intake-independent metabolic role, while cell-specific GFRAL neuron activation revealed a torpor-like state encompassing hypothermia, fuel switching, and stress hormone release.

    Evidence Stereotaxic AP infusion with hyperinsulinemic-euglycemic clamp and GFRAL knockdown; chemogenetic activation of GFRAL+ neurons with metabolomics and transcriptomics

    PMID:38064571 PMID:38507407

    Open questions at the time
    • Efferent pathways from AP GFRAL neurons to liver not anatomically traced
    • Whether torpor-like response is physiologically relevant outside experimental activation is unclear
    • Integration with other glucose-regulatory circuits (e.g., GLP-1) not defined
  11. 2024 High

    BDNF-expressing medial NTS neurons were positioned downstream of GFRAL neurons in a hierarchical circuit required for GDF15-induced weight reduction and fatty acid oxidation, and GFRAL knockdown in an ALS model ameliorated wasting and prolonged survival, linking the pathway to neurodegenerative cachexia.

    Evidence Genetic circuit tracing and conditional neuron ablation/activation for BDNF-mNTS; shRNA-mediated GFRAL knockdown in hSOD1-G93A ALS mice with survival and motor analysis

    PMID:39672239 PMID:39737892

    Open questions at the time
    • How BDNF-mNTS neurons integrate GDF15 versus GLP-1 signals is unknown
    • Therapeutic window for GFRAL blockade in ALS (beneficial weight preservation versus loss of metabolic regulation) not defined
  12. 2026 High

    GDF15–GFRAL signaling was shown to suppress autoimmune T cell responses via a brain-to-spleen neuroimmune circuit involving β-adrenergic signaling and norepinephrine-dependent downregulation of T cell integrins, revealing an immunomodulatory function of GFRAL beyond metabolism.

    Evidence Gfral knockout mice in EAE, neuronal gene delivery, chemogenetic activation, norepinephrine and integrin measurements

    PMID:41540266

    Open questions at the time
    • Whether this neuroimmune axis operates in non-autoimmune inflammatory contexts is untested
    • Identity of the sympathetic relay neurons between brainstem and spleen not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of the ternary GDF15–GFRAL–RET complex, the full intracellular signaling cascade downstream of RET in GFRAL neurons, the precise efferent neural pathways from GFRAL neurons to peripheral organs (liver, sympathetic chain, spleen), and the physiological relevance of GFRAL expression outside the CNS (endothelial cells, platelets).
  • No high-resolution ternary complex structure available
  • Intracellular signaling beyond RET/ERK/AKT phosphorylation in GFRAL neurons remains unmapped
  • Peripheral (non-neuronal) GFRAL functions lack in vivo validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 1
Partners
GDF15MMP14RET
Complex memberships
GFRAL–RET signaling complex

Evidence

Reading pass · 20 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 with high affinity, and genetic deletion of GFRAL abrogates the ability of GDF15 to decrease food intake and body weight in mice fed a high-fat diet. Radioligand binding assay, Gfral knockout mice with in vivo pharmacology (recombinant GDF15 administration) Nature medicine High 28846097 28846098 28846099
2017 GDF15-induced intracellular signaling requires the interaction of GFRAL with the co-receptor RET; GFRAL alone is insufficient and must recruit RET to transduce the GDF15 signal. Cell-based signaling assay (RET co-receptor requirement), co-receptor recruitment experiments Nature medicine High 28846097 28846098 28846099
2017 GFRAL expression is restricted to neurons of the area postrema (AP) and nucleus of the solitary tract (NTS) in the hindbrain of mice, rats, and monkeys, establishing a central (CNS) mechanism for GDF15-mediated food intake reduction. In situ hybridization, immunohistochemistry, regional mRNA expression analysis Nature medicine High 28846097 28846098 28846099
2005 GFRAL (GRAL) protein localizes predominantly to the plasma membrane; overexpression of GFRAL-A protects PC12 cells and hippocampal neurons from serum starvation-induced apoptosis through inhibition of the JNK signaling pathway. Subcellular fractionation/immunofluorescence for localization; cell survival assay with overexpression and JNK pathway analysis Journal of neurochemistry Medium 16086688
2019 GFRAL expressed specifically in AP/NTS neurons mediates resistance to diet-induced obesity; shRNA knockdown of GFRAL specifically in the AP/NTS increased body weight and adiposity proportionally to knockdown efficiency, confirming AP/NTS as the major CNS site of GDF15 action. AAV-shRNA regional knockdown in AP/NTS, quantitative immunostaining, metabolic measurements International journal of obesity High 31152154
2020 An antagonistic anti-GFRAL monoclonal antibody (3P10) prevents the GDF15-driven interaction of RET with GFRAL on the cell surface, blocking RET phosphorylation and downstream signaling. Activation of the GFRAL-RET pathway induces expression of lipid metabolism genes in adipose tissue, and peripheral sympathectomy or loss of adipose triglyceride lipase protects mice from GDF15-induced weight loss, revealing a peripheral sympathetic lipolytic axis downstream of GFRAL. Antagonistic monoclonal antibody, cell-surface receptor interaction assay, chemical sympathectomy, ATGL knockout mice, gene expression in adipose tissue Nature medicine High 32661391
2021 Artificial activation of GFRAL-expressing neurons inhibits feeding, decreases gastric emptying, and promotes conditioned taste aversion. GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), targeting CGRP-expressing (CGRP-PBN) neurons, and silencing CGRP-PBN neurons abrogates the aversive and anorectic effects of GDF-15. Chemogenetic/optogenetic activation of Gfral-Cre neurons, TRAP-Seq transcriptomics, conditional neuron silencing, behavioral assays (conditioned taste aversion, food intake, gastric emptying) Proceedings of the National Academy of Sciences of the United States of America High 33593916
2022 MT1-MMP (MMP14) proteolytically cleaves and inactivates GFRAL, acting as an endogenous negative regulator of GDF15-GFRAL signaling in the context of obesity. Overnutrition-induced obesity increases MT1-MMP activation, suppressing GFRAL-mediated anorectic signaling. Genetic ablation of MT1-MMP specifically in GFRAL+ neurons restores GFRAL expression and reduces weight gain. Proteolytic cleavage assay, conditional MT1-MMP knockout in GFRAL+ neurons, GFRAL immunostaining, in vivo metabolic phenotyping Nature metabolism High 35177851
2022 The GDF15-GFRAL axis mediates cisplatin-induced behavioral fatigue in mice; a neutralizing monoclonal antibody against GFRAL largely prevented cisplatin-induced decrease in voluntary wheel running and accelerated recovery. Neutralizing anti-GFRAL monoclonal antibody, voluntary wheel running behavioral assay, GDF15-Fc administration Brain, behavior, and immunity Medium 36427806
2022 GFRAL is required for mitochondrial stress-induced daytime-restricted anorexia and anxiety-like behavior; in a mouse model of muscle-specific mitochondrial dysfunction, GFRAL mediates GDF15-driven hypothalamic corticotropin-releasing hormone induction and anxiogenic behavior without elevated corticosterone. Gfral knockout mice crossed with muscle-specific mitochondrial dysfunction model, food intake measurements, anxiety behavioral assays, CRH expression analysis Life science alliance Medium 36271504
2024 Acute GDF15 infusion directly into the area postrema activates GFRAL to increase glucose tolerance and insulin sensitivity by lowering hepatic glucose production, independent of changes in food intake, weight, and plasma insulin. GFRAL knockdown in the AP negated both GDF15 and metformin effects on glucose tolerance. Stereotaxic intracerebral infusion into area postrema, hyperinsulinemic-euglycemic clamp, GFRAL knockdown (AAV-shRNA), hepatic glucose production measurement Diabetes High 38064571
2024 Cell-specific activation of GFRAL+ neurons induces a torpor-like state including hypothermia, stress hormone release, shift from glucose to lipid oxidation, impaired insulin sensitivity, impaired glucose tolerance, reduced skeletal muscle glucose uptake, and augmented visceral fat glucose uptake. Chemogenetic/optogenetic cell-specific activation of GFRAL+ neurons, metabolomics, transcriptomics of muscle and fat, glucose uptake measurements Cell reports High 38507407
2020 GFRAL expressed on endothelial cells mediates MIC-1/GDF15-induced proangiogenic signaling via MEK/ERK and PI3K/Akt pathways; siRNA knockdown of GFRAL abrogated MIC-1-induced angiogenic responses in endothelial cells. siRNA knockdown of GFRAL in endothelial cells, angiogenesis assays (tube formation, sprouting), MIC-1 transgenic mouse model, signaling pathway inhibitors Journal of cellular physiology Medium 33151561
2023 GDF-15 inhibits ADP-induced human platelet aggregation through the GFRAL/RET signaling complex expressed on platelets; GFRAL was identified as the binding partner of GDF-15 on platelets by receptor microarray and immunoprecipitation, and GDF-15 inhibits AKT and ERK activation via this complex. Platelet aggregation assay, receptor microarray, immunoprecipitation, RET agonist/inhibitor pharmacology, ERK/AKT pathway analysis Biomolecules Medium 38254638
2024 A population of BDNF-expressing neurons in the medial NTS (BDNF-mNTS) lies downstream of GFRAL/GLP1R neurons and is required for the weight-reducing actions of GDF15; acute activation of BDNF-mNTS neurons reduces food intake and drives fatty acid oxidation. Genetic circuit tracing, conditional neuron ablation/activation (Cre-based), Exendin-4 and GDF15 pharmacology in BDNF-mNTS-specific manipulated mice Nature communications High 39737892
2024 GFRAL silencing by shRNA in the AP/NTS of ALS model mice (hSOD1G93A) induces weight gain, reduces adipose wasting, ameliorates motor function and muscle atrophy, and prolongs survival, indicating that GDF15-GFRAL signaling drives weight loss and lipid metabolism dysfunction in ALS. shRNA-mediated regional GFRAL knockdown in AP/NTS, body weight monitoring, lipolytic gene expression in adipose tissue, motor function tests, survival analysis, microglia depletion (PLX5622) Brain, behavior, and immunity Medium 39672239
2026 GDF15-GFRAL signaling on brainstem neurons suppresses autoimmune T cell responses by inducing β-adrenergic signaling and norepinephrine synthesis in the spleen, leading to decreased integrin expression on T cells required for blood-brain barrier transmigration. Gfral knockout mice in EAE model, neuronal GDF15/GFRAL gene delivery, chemogenetic activation of GFRAL+ neurons, norepinephrine/integrin measurements, T cell flow cytometry Nature immunology High 41540266
2023 GDF15 C-terminal peptide fragments bind the extracellular domain of GFRAL (identified by SPOT peptide arrays) and inhibit GFRAL/RET signaling in cells expressing the receptor complex, revealing the binding interface relevant for antagonist design. SPOT peptide arrays, solid-phase peptide synthesis, functional cell-based GFRAL/RET signaling assay Peptides Medium 37495041
2023 A peptide antagonist of GFRAL (GRASP) binds GFRAL directly (surface plasmon resonance, flow cytometry), blocks GDF15-mediated RET recruitment, and attenuates GDF15-induced nausea and anorexia in rats. Peptide library screen, surface plasmon resonance, flow cytometry, in vivo rat nausea/anorexia model with cisplatin Journal of medicinal chemistry Medium 37506293
2025 Bicyclic peptide tandems that mimic homodimeric GDF15 bind GFRAL with picomolar affinity and inhibit GDF15-GFRAL protein-protein interaction and RET-induced cell signaling in functional assays, with structural data guiding design. Phage display, structure-guided design, biophysical binding assays, functional cell signaling inhibition assay, pharmacokinetic profiling Journal of medicinal chemistry Medium 41066664

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 615 28846097
2017 The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nature medicine 541 28846098
2017 GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nature medicine 536 28846099
2018 The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases. Cell metabolism 331 30184485
2020 Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice. Nature medicine 253 32661391
2020 The GDF15-GFRAL Pathway in Health and Metabolic Disease: Friend or Foe? Annual review of physiology 175 33228454
2020 Insights Into Mechanisms of GDF15 and Receptor GFRAL: Therapeutic Targets. Trends in endocrinology and metabolism: TEM 132 33172749
2018 Uniting GDF15 and GFRAL: Therapeutic Opportunities in Obesity and Beyond. Trends in endocrinology and metabolism: TEM 101 29866502
2021 GFRAL-expressing neurons suppress food intake via aversive pathways. Proceedings of the National Academy of Sciences of the United States of America 73 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 57 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 36 36001956
2024 GFRAL Is Widely Distributed in the Brain and Peripheral Tissues of Mice. Nutrients 32 38474863
2022 Body weight regulation via MT1-MMP-mediated cleavage of GFRAL. Nature metabolism 31 35177851
2020 Upregulated GDF-15 expression facilitates pancreatic ductal adenocarcinoma progression through orphan receptor GFRAL. Aging 31 33201838
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 24 38507407
2022 The GDF15-GFRAL axis mediates chemotherapy-induced fatigue in mice. Brain, behavior, and immunity 22 36427806
2023 Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice. Molecular metabolism 21 37356805
2021 Expression of the Body-Weight Signaling Players: GDF15, GFRAL and RET and their clinical relevance in Gastric Cancer. Journal of Cancer 20 34149933
2024 Fatty Acids Increase GDF15 and Reduce Food Intake Through a GFRAL Signaling Axis. Diabetes 18 37847913
2009 Imprecise transcription termination within Escherichia coli greA leader gives rise to an array of short transcripts, GraL. Nucleic acids research 16 20008510
2025 Ectopic expression of GDF15 in cancer-associated fibroblasts enhances melanoma immunosuppression via the GFRAL/RET cascade. Journal for immunotherapy of cancer 15 40555562
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
2023 GDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex. Biomolecules 9 38254638
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
2024 Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling. Nature communications 8 39737892
2023 Creation of a Peptide Antagonist of the GFRAL-RET Receptor Complex for the Treatment of GDF15-Induced Malaise. Journal of medicinal chemistry 8 37506293
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
2025 Deletion of GFRAL blunts weight lowering effects of FGF21 in female mice. The Journal of endocrinology 3 40167255
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 3 36912475
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 1 41094454
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 Design of Bicyclic Peptide Tandems Mimicking the Homodimeric GDF15 Protein to Inhibit GDF15-GFRaL-RET Complex Cell Signaling. Journal of medicinal chemistry 0 41066664
2025 Inhibition of GDF15/GFRAL: A novel opportunity for the treatment of solid tumors. International immunopharmacology 0 41455368