Affinage

RSPO2

R-spondin-2 · UniProt Q6UXX9

Length
243 aa
Mass
28.3 kDa
Annotated
2026-04-28
53 papers in source corpus 21 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RSPO2 is a secreted signaling protein that functions as a context-dependent modulator of Wnt, BMP, and FGF pathways, with additional roles in integrin-mediated signaling, governing stem cell self-renewal, tissue morphogenesis, and neuromuscular junction formation. Through its furin-like domains, RSPO2 binds LGR4/5/6 receptors and the E3 ubiquitin ligases ZNRF3/RNF43 to regulate Frizzled receptor turnover: in most contexts it potentiates canonical Wnt/β-catenin signaling by promoting Frizzled stabilization (PMID:32457899, PMID:38758792), but it can also stabilize ZNRF3 in an LGR5-dependent manner to suppress Wnt signaling (PMID:24476626) and promote ZNRF3-mediated ubiquitination and degradation of Fzd7 to antagonize noncanonical Wnt/PKC/ERK signaling (PMID:28600110). Beyond Wnt, RSPO2 inhibits BMP receptor signaling to maintain AML stem cell self-renewal (PMID:34407399), antagonizes FGF signaling via its thrombospondin type 1 domain during mesoderm patterning (PMID:32366679), directly engages integrin β3 and LGR4 to activate FAK/Src signaling (PMID:36217544), and acts through LGR5 to promote acetylcholine receptor clustering at neuromuscular junctions (PMID:30206360).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2014 High

    Resolving whether RSPO2 is solely a Wnt agonist, this study revealed that RSPO2 can stabilize ZNRF3 at the membrane via LGR5 to inhibit rather than activate Wnt/β-catenin signaling in colorectal cancer cells, establishing context-dependent duality.

    Evidence Reciprocal Co-IP and Wnt reporter epistasis with LGR5 knockdown in multiple CRC cell lines

    PMID:24476626

    Open questions at the time
    • Whether this inhibitory mode operates in normal colonic epithelium in vivo
    • Structural basis for how LGR5 engagement switches RSPO2 from agonist to antagonist
  2. 2016 Medium

    Extended RSPO2's functional reach beyond canonical Wnt by showing it inhibits PPARγ nuclear translocation and PPARγ-dependent CD36 transcription, reducing oxidized LDL uptake in macrophages.

    Evidence ChIP for PPARγ at CD36 promoter plus knockdown/overexpression in macrophages

    PMID:27571704

    Open questions at the time
    • Which RSPO2 receptor mediates PPARγ inhibition
    • Whether this is Wnt/β-catenin-dependent or represents a distinct signaling branch
  3. 2017 High

    Demonstrated that RSPO2 engages noncanonical Wnt signaling by directly binding Fzd7 and promoting its ZNRF3-mediated ubiquitination and degradation, thereby suppressing PKC/ERK-dependent cell migration.

    Evidence Reciprocal Co-IP, ubiquitination assays, and epistasis with ZNRF3/Fzd7 in cancer cell migration assays

    PMID:28600110

    Open questions at the time
    • Whether other Frizzled family members are similarly targeted
    • In vivo relevance of RSPO2–Fzd7 antagonism in tumor metastasis
  4. 2017 Medium

    Established the RSPO2–LGR4 axis in canonical Wnt activation by showing RSPO2 signals through GPR48/LGR4 to phosphorylate ERK, LRP6, and GSK3β(Ser9) in thyroid cancer cells.

    Evidence Exogenous RSPO2 treatment with LGR4 knockdown and phospho-Western blots

    PMID:29383135

    Open questions at the time
    • Whether LGR4 and LGR5 mediate opposing RSPO2 outputs within the same cell
    • Contribution of ZNRF3/RNF43 in this thyroid cancer context
  5. 2018 High

    Identified a developmental role for RSPO2 at the neuromuscular junction, showing motor neuron–derived Rspo2 signals via Lgr5 to promote AChR clustering and proper NMJ ultrastructure.

    Evidence Tissue-specific genetic rescue of Rspo2−/− mice with immunofluorescence and electron microscopy

    PMID:30206360

    Open questions at the time
    • Whether Rspo2-Lgr5 at the NMJ acts through canonical Wnt or a distinct pathway
    • Role of muscle-derived Rspo2 beyond ultrastructural normalization
  6. 2020 High

    Revealed a Wnt-independent function: the TSP1 domain of Rspo2 inhibits FGF/Mek1/ERK signaling to regulate mesoderm patterning, mechanistically separating this from the furin domain–mediated Wnt activity.

    Evidence Domain deletion/mutagenesis in Xenopus explants with ERK phosphorylation assays

    PMID:32366679

    Open questions at the time
    • Identity of the receptor for the TSP1 domain
    • Whether TSP1-mediated FGF antagonism operates in mammalian systems
  7. 2020 High

    Placed Rspo2 in a HH–Foxf1 transcriptional hierarchy governing tracheal cartilage, and showed genetic cooperation between Rspo2 and Wnt9b for facial morphogenesis via compound knockout synergy.

    Evidence Multiple HH/Gli and Foxf1 conditional mouse mutants with lineage tracing; Wnt9b;Rspo2 compound knockout mice

    PMID:32457899 PMID:33328171

    Open questions at the time
    • Whether RSPO2 acts directly on Sox9+ chondrocyte progenitors or via an intermediate cell type
    • Relative contributions of RSPO2 versus other R-spondins in craniofacial development
  8. 2021 High

    Uncovered a second Wnt-antagonizing mechanism: Rspo2 inhibits TCF3 phosphorylation independently of RNF43/ZNRF3 and LGR4/5 binding, establishing a distinct mode of Wnt antagonism during anteroposterior axis specification.

    Evidence Binding-deficient RSPO2 mutants with TCF3 phosphorylation assays and epistasis in Xenopus

    PMID:34183732

    Open questions at the time
    • The kinase whose activity on TCF3 is blocked by RSPO2
    • Whether this TCF3-dependent mechanism operates in mammals
  9. 2021 Medium

    Defined transcriptional regulation of RSPO2: E2F1 occupancy at the RSPO2 promoter is controlled by DNA methylation at specific CpG sites, providing an epigenetic on/off switch for RSPO2 expression in granulosa cells.

    Evidence Bisulfite sequencing, DNMT1 knockdown, ChIP for E2F1, luciferase reporter

    PMID:34175894

    Open questions at the time
    • Whether this methylation-dependent regulation applies outside the ovarian context
    • Upstream signals that trigger RSPO2 promoter demethylation
  10. 2021 High

    Established a Wnt-independent role for RSPO2 in stem cell biology by showing that autocrine RSPO2 inhibits BMP receptor signaling to maintain AML self-renewal, and separately showed RSPO2 in oocytes interacts with GDF9:BMP15 heterodimers to coordinate Wnt and SMAD2 signaling in granulosa cells.

    Evidence RSPO2 knockdown/overexpression with BMP signaling assays and AML xenograft survival; oocyte-specific conditional knockout with Co-IP of RSPO2–GDF9:BMP15

    PMID:34407399 PMID:40492505

    Open questions at the time
    • Molecular mechanism by which RSPO2 inhibits BMP receptors
    • Whether BMP antagonism requires LGR receptors or is receptor-independent
  11. 2022 High

    Identified RSPO2 as a paracrine inhibitor of adipogenic progenitor maturation via LGR4, linking it to adipose tissue remodeling and systemic insulin resistance.

    Evidence scRNA-seq of adipose tissue, Rspo2 loss-of-function mouse models with metabolic phenotyping and Lgr4 epistasis

    PMID:35027768

    Open questions at the time
    • Whether RSPO2-LGR4 acts through Wnt, BMP, or another downstream pathway in adipocyte progenitors
    • Therapeutic potential of blocking RSPO2 for metabolic disease
  12. 2022 Medium

    Expanded RSPO2's receptor repertoire beyond LGR/ZNRF3 by showing it directly binds integrin β3 and stabilizes it, while simultaneously preventing LGR4 endocytic degradation to activate FAK/Src signaling in ovarian cancer.

    Evidence Co-IP, proximity ligation assay, receptor pulldown, and phosphorylation assays in ovarian cancer cells

    PMID:36217544

    Open questions at the time
    • Structural basis for RSPO2–integrin β3 binding
    • Whether integrin β3 engagement is a general feature of RSPO2 or specific to ovarian cancer
  13. 2022 High

    Demonstrated that RSPO2/RANKL co-signal through LGR4 via Gαq and β-catenin to induce DKK1 and promote osteoclastic premetastatic niche formation, revealing a cooperative ligand-receptor mechanism.

    Evidence GPCR agonist screening, Co-IP, soluble LGR4 decoy receptor in mouse bone metastasis model

    PMID:34847079

    Open questions at the time
    • Whether RSPO2 and RANKL form a ternary complex on LGR4 or signal sequentially
    • Relevance to human bone metastasis
  14. 2024 High

    Identified VDR as a direct transcriptional regulator of Rspo2 via a distal enhancer ~15 kb upstream; deletion of this site abolished calcitriol-mediated Rspo2 induction and downstream MuSK phosphorylation at the NMJ.

    Evidence ChIP-seq of VDR, CRISPR/Cas9 enhancer deletion, MuSK phosphorylation assay

    PMID:38233267

    Open questions at the time
    • Whether VDR-dependent RSPO2 regulation operates in tissues beyond skeletal muscle
    • Therapeutic implications for NMJ diseases
  15. 2024 High

    Placed RSPO2 downstream of the chromatin modifier KAT6A in hippocampal neurons, showing that KAT6A-dependent histone acetylation drives Rspo2 transcription to sustain Wnt signaling required for synaptic plasticity and memory.

    Evidence KAT6A and RSPO2 conditional knockouts in excitatory neurons, AAV-mediated RSPO2 rescue in CA3, behavioral tests

    PMID:38758792

    Open questions at the time
    • Whether RSPO2 acts through LGR4 or LGR5 in hippocampal neurons
    • Whether other R-spondins compensate when RSPO2 is lost in the brain
  16. 2025 High

    Structure-function dissection showed that a mutant furin domain retains LGR4/5/6 binding but loses Wnt-activating capacity, enabling design of signaling-dead RSPO2 peptibodies for targeted drug delivery to LGR-positive cancers.

    Evidence Furin domain mutagenesis with binding affinity and TOPFLASH assays, in vitro cytotoxicity, xenograft efficacy

    PMID:41954225

    Open questions at the time
    • Crystal structure of the signaling-dead mutant bound to LGR
    • Long-term in vivo safety and pharmacokinetics

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for how RSPO2 switches between Wnt agonist and antagonist outputs depending on LGR receptor identity, the receptor mediating TSP1-domain FGF antagonism, and the direct mechanism of BMP receptor inhibition.
  • No crystal structure of RSPO2 in complex with LGR5 versus LGR4 to explain opposing signaling outcomes
  • Identity of the TSP1 domain receptor remains unknown
  • Mechanism by which RSPO2 inhibits BMP receptor signaling is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 7 GO:0098772 molecular function regulator activity 5
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 3
Partners
BMP15FZD7GDF9ITGB3LGR4LGR5RNF43ZNRF3

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 RSPO2 interacts with LGR5 to stabilize membrane-associated ZNRF3, thereby inhibiting Wnt/β-catenin signaling in a LGR5-dependent manner in colorectal cancer cells Co-immunoprecipitation, overexpression/knockdown with Wnt reporter assays, epistasis with LGR5 depletion Nature communications High 24476626
2017 RSPO2 physically interacts with Fzd7 and promotes ZNRF3-mediated ubiquitination and degradation of cell-surface Fzd7, thereby suppressing PKC/ERK noncanonical Wnt signaling and antagonizing Wnt5a-driven cell migration Co-immunoprecipitation, ubiquitination assay, cell migration/invasion assays, epistasis with ZNRF3 and Fzd7 Cancer letters High 28600110
2022 RSPO2 and RANKL signal through LGR4 to promote osteoclastic premetastatic niche formation; RSPO2/RANKL-LGR4 modulates DKK1 via Gαq and β-catenin signaling, and DKK1 facilitates osteoclast precursor recruitment by suppressing LRP5 and upregulating Rnasek GPCR ligand/agonist screening, Co-IP, knockdown/overexpression, decoy receptor (soluble LGR4 ECD) in mouse bone metastasis model The Journal of clinical investigation High 34847079
2022 RSPO2 maintains AML self-renewal by inhibiting BMP receptor signaling in a WNT-independent manner; autocrine RSPO2 prevents differentiation of normal hematopoietic stem cells and primary AML cells RSPO2 knockdown/overexpression, BMP signaling assays, AML xenograft mouse models with survival readout Cell reports High 34407399
2022 RSPO2 is secreted by a subset of CD142+ adipogenic progenitor cells and inhibits maturation of early adipogenic progenitors through the receptor LGR4, leading to adipose tissue hypertrophy and insulin resistance Single-cell RNA-sequencing, loss-of-function mouse models, receptor identification (Lgr4), metabolic phenotyping Nature metabolism High 35027768
2020 Rspo2 inhibits FGF signaling upstream of Mek1 via its thrombospondin type 1 (TSP1) domain, downregulating FGF target genes tbxt/brachyury and cdx4 during Xenopus mesoderm formation; this is distinct from its Furin-like domain-mediated Wnt activity Xenopus ectoderm explant elongation assay, ERK1 phosphorylation assay, domain deletion/mutagenesis, morpholino depletion Development (Cambridge, England) High 32366679
2021 Rspo2 inhibits TCF3/TCF7L1 phosphorylation to antagonize Wnt signaling during Xenopus anteroposterior axis specification, independently of binding to RNF43/ZNRF3 and LGR4/5 Xenopus gain/loss-of-function, domain binding assays (RNF43/ZNRF3 and LGR4/5 binding-deficient mutants), TCF3 phosphorylation assays, epistasis with TCF3 depletion Scientific reports High 34183732
2018 Rspo2 promotes acetylcholine receptor (AChR) clustering and neuromuscular junction (NMJ) formation via its receptor Lgr5; motor neuron-derived Rspo2 plays the major role in AChR clustering while muscle-derived Rspo2 normalizes ultrastructural NMJ features Tissue-specific rescue of Rspo2-/- mice (SMN-specific and muscle-specific expression), immunofluorescence, electron microscopy, gene expression analysis Scientific reports High 30206360
2022 RSPO2 promotes ovarian cancer growth and metastasis through dual receptor signaling: (1) RSPO2-LGR4 interaction prevents endocytic degradation of LGR4 and promotes LGR4-mediated translocation of Src to the plasma membrane; (2) RSPO2 directly binds integrin β3 as a ligand, enhancing integrin stability; both mechanisms potentiate FAK/Src autophosphorylation Co-immunoprecipitation, proximity ligation assay, receptor pulldown, phosphorylation assays, knockdown/overexpression iScience Medium 36217544
2020 A HH-Foxf1-Rspo2 signaling axis governs tracheal cartilage development: HH/Gli signaling maintains Foxf1 expression in splanchnic mesoderm, which in turn supports Rspo2 expression, and Rspo2 potentiates Wnt signaling required for Sox9+ chondrocyte progenitor specification Multiple HH/Gli mouse mutants, lineage tracing, Foxf1 conditional knockout, Rspo2 expression analysis Disease models & mechanisms High 33328171
2020 Wnt9b and RSPO2 cooperate to activate canonical Wnt/β-catenin signaling during mouse facial morphogenesis; compound Wnt9b;Rspo2 double knockout mice display more severe facial defects than either single mutant Compound mouse knockout, ex vivo facial explants, gene expression analysis Frontiers in cell and developmental biology High 32457899
2024 KAT6A regulates Rspo2 transcription in hippocampal CA3 neurons via histone acetylation; KAT6A deficiency reduces RSPO2-Wnt signaling leading to impaired synaptic plasticity and memory deficits; restoring RSPO2 in CA3 rescues Wnt signaling and cognitive deficits in Kat6a mutant mice KAT6A conditional knockout, RSPO2 conditional knockout in excitatory neurons, AAV-mediated RSPO2 re-expression in CA3, Wnt signaling assays, behavioral tests Science advances High 38758792
2022 RSPO2 overexpression suppresses ectopic ossification in a mouse Achilles tendon puncture model by suppressing chondrogenic differentiation; RSPO2 is induced by NF-κB signaling in response to inflammatory stimulation and mechanical loading RSPO2 overexpression in mouse tendon puncture model, chondrogenic differentiation assays in human ligament cells, NF-κB inhibitor experiments Science advances Medium 35984875
2021 miR-181a targets RSPO2 mRNA in mesenchymal stromal cells during chondrogenesis, leading to reduced WNT signaling and increased BMP signaling (phospho-SMAD1/5/9 and SOX9 accumulation), establishing RSPO2 as a coordinator of WNT-BMP signaling crosstalk miR reporter assay (luciferase), miR-181a mimic/inhibitor transfection, Western blot for SMAD1/5/9 phosphorylation and SOX9 Frontiers in cell and developmental biology Medium 34778258
2016 RSPO2 inhibits PPAR-γ nuclear translocation and reduces PPAR-γ binding to the CD36 promoter (assessed by ChIP), thereby suppressing CD36 expression, reducing oxLDL uptake, and inhibiting macrophage apoptosis Flow cytometry, Western blot, chromatin immunoprecipitation (ChIP), Rspo2 knockdown/overexpression in macrophages Molecular medicine reports Medium 27571704
2024 Calcitriol induces Rspo2 expression via vitamin D receptor (VDR) binding to a region ~15 kb upstream of Rspo2; deletion of this VDR-binding site by CRISPR/Cas9 abolishes calcitriol-mediated Rspo2 induction and MuSK phosphorylation at the neuromuscular junction ChIP-seq of VDR, CRISPR/Cas9 deletion of VDR-binding site, RNA-seq, MuSK phosphorylation assay, Chrne KO mouse model Neurotherapeutics High 38233267
2021 RSPO2 knockdown in oocytes disrupts granulosa cell development and oocyte competence; RSPO2 (expressed in oocytes) physically interacts with GDF9:BMP15 heterodimers and its effects involve crosstalk between CTNNB1- and SMAD2-dependent pathways in granulosa cells Conditional oocyte-specific Rspo2 knockout, Co-immunoprecipitation (RSPO2 with GDF9:BMP15), transcriptomic analysis, pathway inhibitor experiments Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 40492505
2021 RSPO2 silence in nasopharyngeal carcinoma increases ZNRF3 expression and reduces Hedgehog/Gli1 signaling; ZNRF3 knockdown or Gli1 overexpression reverses the anti-tumor effects of RSPO2 depletion, placing RSPO2 upstream of ZNRF3/Hedgehog-Gli1 siRNA knockdown, epistasis rescue by ZNRF3 knockdown and Gli1 overexpression, in vivo xenograft Life sciences Medium 34273374
2025 PALMD interacts with RSPO2 and facilitates its secretion, enabling paracrine activation of Wnt/β-catenin signaling to promote colorectal cancer stemness and tumor growth; pharmacologic or antibody blockade of RSPO2 attenuates PALMD-mediated Wnt activation Co-immunoprecipitation (PALMD-RSPO2), gene knockdown/overexpression, Wnt reporter assay, organoid models, in vivo xenograft bioRxivpreprint Medium
2025 A mutant RSPO2 furin domain retains high-affinity binding to LGR4/5/6 but lacks Wnt/β-catenin signaling activity; this property was used to create drug-conjugated peptibodies that deliver cytotoxins specifically to LGR4/5/6-positive cancer cells Binding affinity assays, TOPFLASH Wnt reporter assay, mutagenesis of furin domain, in vitro cytotoxicity, in vivo xenograft Journal of medicinal chemistry High 41954225
2017 RSPO2 activates the β-catenin pathway through GPR48/LGR4, inducing phosphorylation of ERK, LRP6, and GSK3β (serine 9); downregulation of GPR48/LGR4 decreases β-catenin pathway activity in thyroid cancer cells Exogenous RSPO2 treatment, LGR4 knockdown, Western blot for phospho-ERK/LRP6/GSK3β and β-catenin Oncotarget Medium 29383135
2021 DNA methylation of RSPO2 promoter at -758/-749 and -563/-553 CpG regions controls RSPO2 transcription by regulating occupancy of transcription factor E2F1; hypomethylation facilitates E2F1 binding and increases RSPO2 expression in granulosa cells Bisulfite sequencing, DNMT1 knockdown, DNMT inhibitor treatment, ChIP for E2F1 at RSPO2 promoter, luciferase reporter assay Cell death & disease Medium 34175894

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 RSPO2-LGR5 signaling has tumour-suppressive activity in colorectal cancer. Nature communications 105 24476626
2022 RSPO2 and RANKL signal through LGR4 to regulate osteoclastic premetastatic niche formation and bone metastasis. The Journal of clinical investigation 68 34847079
2015 RSPO2 Enhances Canonical Wnt Signaling to Confer Stemness-Associated Traits to Susceptible Pancreatic Cancer Cells. Cancer research 65 25769727
2017 RSPO2 suppresses colorectal cancer metastasis by counteracting the Wnt5a/Fzd7-driven noncanonical Wnt pathway. Cancer letters 59 28600110
2022 Identification of a regulatory pathway inhibiting adipogenesis via RSPO2. Nature metabolism 56 35027768
2012 Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary epithelial cells. Journal of cellular physiology 46 21732367
2018 Identification of RSPO2 Fusion Mutations and Target Therapy Using a Porcupine Inhibitor. Scientific reports 40 30250044
2016 Identification and Functional Characterization of RSPO2 as a Susceptibility Gene for Ossification of the Posterior Longitudinal Ligament of the Spine. American journal of human genetics 39 27374772
2021 DNA methylation mediated RSPO2 to promote follicular development in mammals. Cell death & disease 34 34175894
2022 RSPO2 defines a distinct undifferentiated progenitor in the tendon/ligament and suppresses ectopic ossification. Science advances 33 35984875
2019 RSPO2 gene rearrangement: a powerful driver of β-catenin activation in liver tumours. Gut 26 30901310
2023 RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities. Genes & diseases 24 37692504
2017 MicroRNA-493 suppresses hepatocellular carcinoma tumorigenesis through down-regulation of anthrax toxin receptor 1 (ANTXR1) and R-Spondin 2 (RSPO2). Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 28651234
2018 RSPO2 enhances cell invasion and migration via the WNT/β-catenin pathway in human gastric cancer. Journal of cellular biochemistry 21 30362605
2021 RSPO2 inhibits BMP signaling to promote self-renewal in acute myeloid leukemia. Cell reports 20 34407399
2010 An insertion in the RSPO2 gene correlates with improper coat in the Portuguese water dog. The Journal of heredity 20 20562213
2020 Ablation of PKM2 ameliorated ER stress-induced apoptosis and associated inflammation response in IL-1β-treated chondrocytes via blocking Rspo2-mediated Wnt/β-catenin signaling. Journal of cellular biochemistry 19 31916291
2020 Disruption of a hedgehog-foxf1-rspo2 signaling axis leads to tracheomalacia and a loss of sox9+ tracheal chondrocytes. Disease models & mechanisms 19 33328171
2020 miR-196b-5p Promotes Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells via Targeting RSPO2. Cancer management and research 19 33402849
2022 Suppression of Wnt/β-Catenin Signaling Is Associated with Downregulation of Wnt1, PORCN, and Rspo2 in Alzheimer's Disease. Molecular neurobiology 18 36215026
2016 RSPO2 enriches LGR5(+) spheroid colon cancer stem cells and promotes its metastasis by epithelial-mesenchymal transition. American journal of translational research 16 27158331
2019 Identification of a novel PRR15L-RSPO2 fusion transcript in a sigmoid colon cancer derived from superficially serrated adenoma. Virchows Archiv : an international journal of pathology 14 31209633
2020 Canonical WNT/β-Catenin Signaling Activated by WNT9b and RSPO2 Cooperation Regulates Facial Morphogenesis in Mice. Frontiers in cell and developmental biology 13 32457899
2020 A 50-kb deletion disrupting the RSPO2 gene is associated with tetradysmelia in Holstein Friesian cattle. Genetics, selection, evolution : GSE 12 33176673
2017 Upregulation of RSPO2-GPR48/LGR4 signaling in papillary thyroid carcinoma contributes to tumor progression. Oncotarget 12 29383135
2024 KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3. Science advances 11 38758792
2020 Rspo2 antagonizes FGF signaling during vertebrate mesoderm formation and patterning. Development (Cambridge, England) 11 32366679
2018 Differential effects of spinal motor neuron-derived and skeletal muscle-derived Rspo2 on acetylcholine receptor clustering at the neuromuscular junction. Scientific reports 11 30206360
2021 MiR-181a Targets RSPO2 and Regulates Bone Morphogenetic Protein - WNT Signaling Crosstalk During Chondrogenic Differentiation of Mesenchymal Stromal Cells. Frontiers in cell and developmental biology 10 34778258
2019 T5224, RSPO2 and AZD5363 are novel drugs against functional pituitary adenoma. Aging 10 31655798
2025 RSPO2 Coordinates with GDF9:BMP15 Heterodimers to Promote Granulosa Cell and Oocyte Development in Mice. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 40492505
2023 Astaxanthin prevents osteoarthritis by blocking Rspo2-mediated Wnt/β-catenin signaling in chondrocytes and abolishing Rspo2-related inflammatory factors in macrophages. Aging 9 37354487
2021 Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-497-5p inhibit RSPO2 and accelerate OPLL. Life sciences 9 33857573
2022 miR-497-5p-RSPO2 axis inhibits cell growth and metastasis in glioblastoma. Journal of Cancer 8 35281864
2022 RSPO2 promotes progression of ovarian cancer through dual receptor-mediated FAK/Src signaling activation. iScience 8 36217544
2016 Rspo2 suppresses CD36-mediated apoptosis in oxidized low density lipoprotein-induced macrophages. Molecular medicine reports 8 27571704
2023 Rspo2 exacerbates rheumatoid arthritis by targeting aggressive phenotype of fibroblast-like synoviocytes and disrupting chondrocyte homeostasis via Wnt/β-catenin pathway. Arthritis research & therapy 7 37946278
2021 RSPO2 silence inhibits tumorigenesis of nasopharyngeal carcinoma by ZNRF3/Hedgehog-Gli1 signal pathway. Life sciences 6 34273374
2024 Calcitriol ameliorates motor deficits and prolongs survival of Chrne-deficient mouse, a model for congenital myasthenic syndrome, by inducing Rspo2. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 4 38233267
2023 Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/β-catenin signaling pathway. Gastroenterologia y hepatologia 4 37437654
2021 Rspo2 inhibits TCF3 phosphorylation to antagonize Wnt signaling during vertebrate anteroposterior axis specification. Scientific reports 4 34183732
2022 Tracing the Origin of the RSPO2 Long-Hair Allele and Epistatic Interaction between FGF5 and RSPO2 in Sapsaree Dog. Genes 3 35052442
2021 Evaluation of WNT Signaling Pathway Gene Variants WNT7B rs6519955, SFRP4 rs17171229 and RSPO2 rs611744 in Patients with Dupuytren's Contracture. Genes 3 34573275
2025 The RSPO2 gene is associated with bilateral anterior amelia in Chihuahuas. Mammalian genome : official journal of the International Mammalian Genome Society 2 40131457
2025 Screening, expression, and functional validation of camelid-derived nanobodies targeting RSPO2. Veterinary immunology and immunopathology 1 40179630
2024 Identification of Rare EIF3E::RSPO2 Fusion in Recurrent and Aggressive Urachal Adenocarcinoma. Genes, chromosomes & cancer 1 38884183
2026 RSPO2-Based Peptibodies Conjugated with Pyrrolobenzodiazepine Dimer or Camptothecin Analogs Demonstrate Potent Antitumor Activity by Targeting the Three Receptors LGR4/5/6 in Colorectal Cancer and Neuroblastoma. Journal of medicinal chemistry 0 41954225
2026 Multifaceted role of RSPO2: Epigenetics, immunoregulatory, and therapeutic insights in colorectal cancer. Biochimica et biophysica acta. Reviews on cancer 0 42031178
2025 RSPO2-based peptibodies conjugated with pyrrolobenzodiazepine dimer or camptothecin analogs demonstrate potent anti-tumor activity by targeting the three receptors LGR4/5/6. bioRxiv : the preprint server for biology 0 40894780
2025 Hierarchical clustering defines hypermethylated RSPO2 as early-stage potential biomarker in colorectal cancer. Global medical genetics 0 41142323
2025 Leucine Attenuates Osteoarthritis via mTORC1/LXRα-Mediated Macrophage Reprogramming and Rspo2/β-Catenin Axis Suppression. Cartilage 0 41200799
2025 Association Between Gene Polymorphisms of RSPO2 of the Wnt Signaling Pathway and Schizophrenia in the Korean Population. Psychiatry investigation 0 41382343
2024 RETRACTED: RSPO2-associated mitochondrial metabolism defines molecular subtypes with distinct clinical and immune features in esophageal cancer. Environmental toxicology 0 38491805