Affinage

PKP2

Plakophilin-2 · UniProt Q99959

Length
881 aa
Mass
97.4 kDa
Annotated
2026-06-10
66 papers in source corpus 15 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PKP2 encodes plakophilin-2, a dynamic scaffold protein of the cardiomyocyte intercalated disc whose tension-dependent membrane recruitment integrates it into the desmosomal macromolecular complex shared between the DSG2 and N-cadherin interactomes. PKP2 physically bridges desmosomal and electrical machinery, interacting with desmoplakin and connexin-43; ARVC-associated truncation mutants fail to reach cell-cell junctions and lose these interactions, reducing Cx43 abundance (PMID:19084810), while truncated PKP2 in vivo causes dose-dependent remodeling of desmosomal components (desmocollin-2, plakoglobin, desmin, β-catenin) and the conduction proteins Cx43 and Nav1.5 (PMID:27412010). Its localization is controlled by post-translational and regulatory inputs: C-TAK1 phosphorylates PKP2 to create a 14-3-3-binding site governing subcellular distribution (PMID:12941695), and CASK negatively regulates its accumulation at intercalated discs. Beyond junctional architecture, PKP2 loss in cardiomyocytes triggers a broad pathological cascade — loss of nuclear envelope integrity with DNA damage and paracrine H2O2-driven oxidant production (PMID:35959657), downregulation of oxidative phosphorylation via reduced PPARGC1A/PGC1α, transcriptional upregulation of inflammatory/immune pathways (PMID:33536940), and induction of senescence in neighboring non-myocytes — collectively establishing the arrhythmogenic cardiomyopathy substrate. PKP2 mutations cause arrhythmogenic cardiomyopathy, and AAV-mediated PKP2 restoration rescues junctional protein levels, sodium conduction, contractility, and adverse fibrotic and transcriptional remodeling in mutant iPSC-cardiomyocytes and in vivo (PMID:38665939, PMID:38499690). In a distinct context, PKP2 acts in tumor cells as a Wnt/β-catenin target and feedback antagonist (PMID:29044515) and, when methylated by PRMT1, stabilizes β-catenin to promote NHEJ-mediated DNA repair and radiation resistance (PMID:33742119).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2003 High

    Established the first post-translational control point for PKP2 localization, showing its membrane targeting is a regulated rather than constitutive property.

    Evidence C-TAK1 binding-motif mutagenesis and in vivo phosphorylation assays mapping a 14-3-3-binding site

    PMID:12941695

    Open questions at the time
    • Did not address the cardiac intercalated-disc context
    • Functional consequence of altered localization on junction assembly not tested
  2. 2008 Medium

    Connected ARVC truncation mutations to a molecular mechanism by showing they prevent junctional targeting and loss of binding to desmoplakin and connexin-43.

    Evidence Adenoviral expression of PKP2 truncation mutants in neonatal rat ventricular myocytes with Co-IP and immunofluorescence

    PMID:19084810

    Open questions at the time
    • Two mutants only; broader mutational spectrum untested
    • Co-IP without reciprocal or structural validation of the interaction interface
  3. 2016 Medium

    Demonstrated in vivo that truncated PKP2 disrupts the entire intercalated-disc protein composition, linking a single defective subunit to coordinated desmosomal and electrical remodeling.

    Evidence Transgenic mouse expressing truncated PKP2 with immunofluorescence, western blot, echocardiography and electrophysiology

    PMID:27412010

    Open questions at the time
    • Dominant-negative vs haploinsufficiency mechanism not resolved
    • Order of molecular events leading to disc disassembly unclear
  4. 2017 Medium

    Placed PKP2 within Wnt/β-catenin signaling as both a transcriptional target and a feedback antagonist, extending its role beyond structural scaffolding.

    Evidence Reporter assays with mapped TCF binding sites and functional antagonism in HEK-293T and fibroblast systems

    PMID:29044515

    Open questions at the time
    • Relevance to cardiomyocyte biology not addressed
    • Mechanism of β-catenin antagonism not defined
  5. 2021 Medium

    Revealed a cancer-cell function in which PRMT1-methylated PKP2 stabilizes β-catenin and promotes NHEJ DNA repair, driving radiation resistance.

    Evidence CRISPR screen, mass-spectrometry detection of arginine methylation, Co-IP and NHEJ functional assays in lung cancer cells

    PMID:33742119

    Open questions at the time
    • Methylated arginine residue's structural role unmapped
    • Whether this axis operates in cardiomyocytes unknown
  6. 2021 Medium

    Linked PKP2 abundance to suppression of inflammatory/immune transcriptional programs in cardiomyocytes, defining a non-structural consequence of PKP2 loss.

    Evidence Cardiomyocyte-specific tamoxifen-inducible KO with RiboTag translatome profiling and GTEx cross-validation

    PMID:33536940

    Open questions at the time
    • Mechanism linking PKP2 loss to inflammatory transcription not defined
    • Causal contribution to disease vs bystander effect unresolved
  7. 2022 High

    Identified nuclear envelope disruption, DNA damage, and paracrine oxidant production as early consequences of PKP2 loss, expanding the disease model from junctional to nuclear/metabolic dysfunction.

    Evidence Proteomics, RNA-seq, TEM across ARVC biopsies, cardiac-specific Pkp2 KO mice and PKP2-deficient hiPSC-CMs

    PMID:35959657

    Open questions at the time
    • Mechanistic link between a disc protein and nuclear envelope integrity unresolved
    • How H2O2 propagates damage to neighboring cells not fully defined
  8. 2023 High

    Provided proof-of-concept that PKP2 gene supplementation reverses arrhythmic and contractile substrate, establishing PKP2 deficiency as causal and correctable.

    Evidence AAV transduction of mutant iPSC-CMs, engineered human myocardium, and heterozygous Pkp2 knock-in mice with electrophysiology and contractility readouts

    PMID:38665939

    Open questions at the time
    • Durability and dosing window in human disease unaddressed
    • Whether nuclear/metabolic defects are also rescued not tested here
  9. 2024 High

    Showed AAV9-PKP2 corrects structure, arrhythmia, fibrosis, and broad transcriptional networks in vivo, demonstrating systemic reversibility beyond desmosomes.

    Evidence AAV9 delivery in cardiac-specific Pkp2 KO mice with echocardiography, ECG, histology and RNA-seq

    PMID:38499690

    Open questions at the time
    • Mechanism of transcriptional network normalization not dissected
    • Reversibility of established late-stage fibrosis unclear
  10. 2025 Medium

    Defined PKP2 as a tension-dependent dynamic disc component within the DSG2/N-cadherin interactome, anchoring its scaffolding role in mechanobiology.

    Evidence Proximity-labeling mass spectrometry and tension-dependence assays in neonatal cardiomyocytes (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Molecular sensor of tension upstream of PKP2 recruitment unknown
  11. 2025 Medium

    Identified CASK as a negative regulator of PKP2 junctional accumulation, adding a counter-regulatory input whose dysregulation contributes to mutant phenotypes.

    Evidence AAV CASK knockdown in neonatal rat hearts, imaging, proteomics, EM and mechano-SICM in NRVM and PKP2+/- hiPSC-CMs (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Direct vs indirect mechanism of CASK action on PKP2 not resolved
  12. 2025 Medium

    Extended PKP2 disease biology to metabolic failure, showing PGC1α-dependent OXPHOS suppression and impaired substrate handling that limit contractility.

    Evidence RNA-seq, Seahorse respirometry, metabolomics and PPARGC1A/AAV9 rescue in hiPSC-CMs, mouse and human hearts (preprints)

    Open questions at the time
    • Preprints, not peer-reviewed
    • How PKP2 loss represses PPARGC1A mechanistically is unknown
  13. 2025 Medium

    Established that PKP2 loss in cardiomyocytes drives paracrine senescence and premature epigenetic aging of cardiac non-myocytes.

    Evidence Multiplex imaging, cytokine arrays, epigenetic clocks and spatial transcriptomics in cardiac-specific PKP2 KO mice (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Signal mediating cardiomyocyte-to-non-myocyte senescence not identified
  14. 2025 Medium

    Used tissue-specific epistasis to show cardiomyocyte PKP2 loss is required for ACM pathogenesis while EPDC loss alone is insufficient, and implicated B cells in early inflammation.

    Evidence Cardiomyocyte-, EPDC-, and combined-specific inducible KO mice with scRNA-seq, flow cytometry and B-cell depletion

    PMID:42246055

    Open questions at the time
    • Cell-type crosstalk mediating EPDC SASP not defined
    • B-cell antigen and mechanism of recruitment unknown
  15. 2025 Medium

    Linked epicardial PKP2 loss to fatty-fibrotic remodeling through EMT, IGF2/CEBPA-driven adipogenesis and Wnt/interferon/Rho dysregulation.

    Evidence iPSC-derived epicardial cells (CRISPR KO and patient lines), RNA-seq, lipid assays and recombinant IGF2 treatment

    PMID:41145823

    Open questions at the time
    • In vivo relevance of IGF2/CEBPA axis untested
    • Connection to cardiomyocyte-required pathogenesis unresolved
  16. 2025 Medium

    Showed AAV9-PKP2 reverses fibrosis by reprogramming activated fibroblasts to quiescent states, identifying Ptprc as a regulator of this conversion.

    Evidence Pkp2-KO rat model with AAV9-PKP2 delivery and single-cell RNA sequencing of fibroblast states

    PMID:40979216

    Open questions at the time
    • Direct role of Ptprc not functionally validated
    • Whether fibroblast reprogramming is PKP2-cell-autonomous unclear
  17. 2026 Medium

    Defined biallelic loss-of-function mechanisms in patients, showing distinct mutations (nuclear aggregation vs exon skipping) synergize to inactivate PKP2 and disrupt desmosomal integrity.

    Evidence MiniGene splicing assays, RT-PCR, immunofluorescence localization and cycloheximide chase

    PMID:41535644

    Open questions at the time
    • Functional cardiac phenotype not directly assessed
    • Generalizability beyond this kindred unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular link connecting a junctional scaffold protein to nuclear envelope integrity, PGC1α-dependent metabolism, and paracrine senescence remains undefined.
  • No mechanism connecting PKP2 loss to PPARGC1A repression
  • Signal driving non-myocyte senescence unidentified
  • Tension-sensing machinery upstream of PKP2 recruitment unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2
Pathway
R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 2 R-HSA-73894 DNA Repair 2
Partners
CASKCDH2CTNNB1DSG2DSPGJA1PRMT1
Complex memberships
desmosomeintercalated disc

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 C-TAK1 (Cdc25C-associated kinase 1) phosphorylates PKP2, generating a 14-3-3-binding site that influences PKP2 subcellular localization. This was established using mutational analysis of C-TAK1 binding motifs and in vivo phosphorylation assays, identifying PKP2 as a novel C-TAK1 substrate. Mutational approach disrupting C-TAK1 binding, in vivo phosphorylation assays, 14-3-3 binding site mapping The EMBO journal High 12941695
2008 ARVC-associated truncation mutants of PKP2 (R79x and 179fs) fail to localize to sites of cell-cell apposition in neonatal rat ventricular myocytes. Early truncation at position 79 prevents physical interaction of PKP2 with both desmoplakin (DP) and connexin-43 (Cx43), and R79x expression reduced Cx43 abundance and correlated with loss of HSP90 expression. Adenoviral expression of mutant PKP2 constructs in neonatal rat ventricular myocytes, co-immunoprecipitation, immunofluorescence localization Heart rhythm Medium 19084810
2016 Expression of truncated PKP2 (PKP2-Ser329) in transgenic mice causes dose-dependent reduction and remodeling of desmosomal proteins (Desmocollin-2, Plakoglobin, native PKP2, Desmin, β-Catenin) and electrical coupling proteins (Connexin 43, Nav1.5), establishing that truncated PKP2 disrupts the molecular composition of the intercalated disc. Transgenic mouse model with truncated PKP2, immunofluorescence, western blot, echocardiography, electrophysiology Human molecular genetics Medium 27412010
2017 PKP2 is a direct transcriptional target of the Wnt/β-catenin pathway, induced via three TCF binding sites in the PKP2 gene promoter and one in an enhancer 20 kb upstream of the transcription start site. Furthermore, Plakophilin-2 antagonizes Wnt/β-catenin transcriptional activity in HEK-293T cells, suggesting it acts as an intracellular feedback inhibitor of the pathway. Transcriptomic analysis, reporter assays, ChIP or promoter binding site analysis in normal and colon cancer-associated fibroblasts, HEK-293T overexpression assay International journal of cancer Medium 29044515
2021 PRMT1 methylates PKP2 at an arginine residue; methylated PKP2 stabilizes β-catenin by recruiting USP7, which then induces LIG4 expression and promotes non-homologous end-joining (NHEJ) DNA repair, thereby driving radiation resistance in lung cancer cells. CRISPR/Cas9 library screen, mass spectrometry identification of arginine methylation, co-immunoprecipitation, functional assays of NHEJ repair, pharmacologic inhibition of PRMT1 Oncogene Medium 33742119
2022 PKP2 deficiency in cardiomyocytes causes loss of nuclear envelope integrity, which leads to DNA damage and excess oxidant production (superoxide and H2O2) under baseline and mechanical stress conditions. PKP2-deficient cells release H2O2 extracellularly, causing DNA damage in neighboring myocytes in a paracrine manner. Early transcriptional downregulation of electron transport chain proteins precedes left ventricular dysfunction. High-resolution mass spectrometry, RNA sequencing, transmission electron microscopy of ARVC patient biopsies; multiple imaging and biochemical techniques in cardiac-specific Pkp2 knockout mice and PKP2-deficient hiPSC-derived cardiomyocytes Circulation High 35959657
2021 In adult cardiac myocytes, PKP2 transcript abundance is transcriptionally linked to genes coding for inflammatory/immune response molecules. Loss of PKP2 in cardiomyocytes (PKP2cKO mice) upregulates a large set of transcripts associated with inflammatory/immune pathways, inversely correlated with PKP2 abundance in human cardiac transcriptomes. Cardiac-specific tamoxifen-activated PKP2-knockout mice crossed with RiboTag line; cardiomyocyte-specific ribosome-resident transcriptome profiling; GTEx human transcriptome correlation analysis Frontiers in physiology Medium 33536940
2023 AAV-mediated delivery of PKP2 in PKP2 mutant iPSC-derived cardiomyocytes restored junctional protein levels (which were reduced by the mutation), improved sodium conduction (rescuing arrhythmic substrate), and enhanced contractile function. In heterozygous Pkp2 knock-in mice, AAV9-PKP2 prevented cardiac dysfunction at 12 months, confirming restoration of desmosomal integrity and cardiac function in vivo. AAV transduction of PKP2c.2013delC/WT iPSC-derived cardiomyocytes, engineered human myocardium, heterozygous Pkp2c.1755delA knock-in mice; electrophysiology, contractility assays, immunostaining of junctional proteins Nature cardiovascular research High 38665939
2024 AAV9-mediated restoration of PKP2 in cardiac-specific Pkp2 knockout mice rescues desmosome and gap junction structure, prevents right ventricular dilation, reduces ventricular arrhythmias, and reverses adverse fibrotic remodeling. RNA sequencing shows AAV9:PKP2 causes broad correction of PKP2-associated transcriptional networks beyond desmosomes. AAV9 gene delivery in cardiac-specific Pkp2 KO mice; echocardiography, electrocardiography, histology, RNA sequencing Communications medicine High 38499690
2025 In exercise-trained PKP2-deficient (PKP2cKO) cardiomyocytes, the pool of sarcolemmal β1-adrenergic receptors (β1-ARs) is decreased compared with exercise-trained controls (where it increases). Intracellular (dyad-associated) β1-ARs remain available in trained PKP2cKO myocytes, as shown by OCT3 knockdown that abolished norepinephrine (non-membrane-permeable) response but not isoproterenol (membrane-permeable) response. Additionally, sympathetic nerve terminal abundance and distribution are heterogeneous in trained PKP2cKO hearts. Expansion microscopy and structured illumination microscopy of β1-ARs; shRNA knockdown of OCT3; Ca2+ transient dynamics with isoproterenol vs norepinephrine; sympathetic terminal distribution imaging Heart rhythm Medium 40383179
2024 PKP2 is a direct target of miR-7-5p; overexpression of miR-7-5p reduces PKP2 protein levels and enhances radiosensitivity in A549 NSCLC cells by increasing DNA damage (γ-H2AX foci) and inhibiting NHEJ repair. Overexpression of PKP2 rescues the radiosensitizing effects of miR-7-5p, confirming the miR-7-5p/PKP2 regulatory axis. Clonogenic assays, CCK-8 assays, immunofluorescence (γ-H2AX), western blotting, reporter gene assays (luciferase 3'UTR validation) Scientific reports Medium 40374728
2025 PKP2 deficiency in cardiomyocytes disrupts oxidative phosphorylation (OXPHOS) gene expression through reduced PPARGC1A (PGC1α) expression, leading to decreased mitochondrial spare capacity in PKP2 mutant hiPSC-CMs and explanted human hearts. Induction of PPARGC1A expression partially restored OXPHOS component expression and improved contractility in PKP2 mutant cells. RNA sequencing of hiPSC-CMs and human explanted hearts; mitochondrial spare capacity (Seahorse) assay; PPARGC1A overexpression rescue experiments bioRxivpreprint Medium
2025 PKP2 deficiency in cardiomyocytes causes impaired lipid homeostasis, glycolysis, and glucose oxidation, with specific metabolic defects linked to poor contractility of cardiomyocytes. AAV9:PKP2 restoration improved contractility, electrophysiological properties, and Ca2+ transients, while pharmacologic metabolic enhancers improved contractility but not electrophysiology, indicating differential sensitivity of PKP2-dependent functions to metabolic perturbation. Steady-state metabolomics in PKP2-deficient mouse hearts and hiPSC-CMs; AAV9:PKP2 gene rescue; pharmacologic metabolic enhancement; contractility and Ca2+ transient measurement bioRxivpreprint Medium
2025 Loss of PKP2 expression specifically in cardiomyocytes (PKP2cKO) is sufficient to induce senescence-associated heterochromatin foci (SAHFs), p21 staining, and senescence-associated secretory phenotype (SASP) cytokines in neighboring non-myocyte cardiac resident cells, as well as premature epigenetic aging of the heart. Conventional and multiplex imaging, cytokine arrays, epigenetic clocks, spatial transcriptomics, expansion and structured illumination microscopy in cardiac-specific PKP2 KO mice bioRxivpreprint Medium
2025 CASK (calcium/calmodulin-dependent serine protein kinase) negatively regulates PKP2 localization at intercalated discs; CASK knockdown increases PKP2 accumulation at cell contacts and promotes desmosome-like structure formation. In PKP2+/- hiPSC-CMs, CASK expression is increased, and CASK depletion rescues PKP2 accumulation at contacts and improves stress resistance. AAV-mediated CASK knockdown in neonatal rat hearts, high-resolution imaging, proteomics, electron microscopy, mechano-SICM in NRVM and PKP2+/- hiPSC-CMs bioRxivpreprint Medium
2025 PKP2 is a dynamic protein at the intercalated disc of cardiomyocytes whose membrane recruitment is tension-dependent. Proximity labeling mass spectrometry identified PKP2 among the most abundant proteins shared between the DSG2 and N-cadherin interactomes in cardiomyocytes, establishing PKP2 as a component of the intercalated disc macromolecular complex. Proximity labeling (BioID/TurboID) combined with quantitative mass spectrometry in cultured neonatal cardiomyocytes; tension-dependence assay bioRxivpreprint Medium
2025 PKP2 deficiency in epicardium-derived cells (EPDCs) facilitates emergence of a pro-inflammatory, senescence-associated secretory phenotype (SASP) fibroblast population; however, cardiomyocyte involvement is required for ACM pathogenesis, as EPDC-specific Pkp2 deletion alone does not elicit a pathological phenotype. B-cell depletion delays early inflammatory and fibrosis response in Pkp2-deficient hearts. Tissue-specific tamoxifen-inducible Cre transgenic mice (cardiomyocyte-specific, EPDC-specific, and combined KO); single-cell RNA sequencing; flow cytometry; immunohistochemistry; antibody-mediated B-cell depletion Circulation. Heart failure Medium 42246055
2025 PKP2 deficiency in iPSC-derived epicardial cells (hPSC-EPCs) causes enhanced epithelial-to-mesenchymal transition, increased lipid accumulation, and a fibrotic phenotype. RNA-seq of ACM hPSC-EPCs reveals dysregulation of Wnt, interferon, and Rho GTPase signaling, upregulation of IGF2 and the adipogenic transcription factor CEBPA. Recombinant IGF2 treatment of control and PKP2KO hPSC-EPCs enhanced CEBPA expression, implicating IGF signaling in fatty-fibro remodeling. iPSC differentiation into epicardial cells, CRISPR/Cas9 KO and patient-derived mutant lines, RNA-seq, lipid accumulation assays, recombinant IGF2 treatment Communications biology Medium 41145823
2025 AAV9-PKP2 gene therapy in Pkp2-knockout rats attenuated cardiac fibrosis by inducing phenotypic conversion of activated profibrotic cardiac fibroblasts into quiescent antifibrotic states, with Ptprc (protein tyrosine phosphatase receptor type C) identified as a key regulator of this reprogramming via single-cell RNA sequencing. Pkp2-knockout rat model, AAV9-PKP2 delivery, single-cell RNA sequencing, fibroblast phenotyping, bioinformatics MedComm Medium 40979216
2026 A PKP2 frameshift mutation (c.1125_1132del, paternal) causes nuclear aggregation of the truncated PKP2 protein (aberrant localization confirmed by immunofluorescence), while a splice-site variant (c.224-3 C>G, maternal) causes exon 2 skipping and protein truncation. Both defects synergistically disrupt desmosomal integrity in cardiomyocytes via biallelic inactivation. MiniGene splicing assays, RT-PCR splice validation, immunofluorescence microscopy of subcellular localization, cycloheximide chase for protein stability Functional & integrative genomics Medium 41535644

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Recessive arrhythmogenic right ventricular dysplasia due to novel cryptic splice mutation in PKP2. Human mutation 68 17041889
2003 Immunohistochemical localization of plakophilins (PKP1, PKP2, PKP3, and p0071) in primary oropharyngeal tumors: correlation with clinical parameters. Human pathology 62 12827610
2003 Functional analysis of C-TAK1 substrate binding and identification of PKP2 as a new C-TAK1 substrate. The EMBO journal 59 12941695
2023 Therapeutic efficacy of AAV-mediated restoration of PKP2 in arrhythmogenic cardiomyopathy. Nature cardiovascular research 58 38665939
2022 Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC. Circulation 58 35959657
2008 Characterization of the molecular phenotype of two arrhythmogenic right ventricular cardiomyopathy (ARVC)-related plakophilin-2 (PKP2) mutations. Heart rhythm 46 19084810
2024 AAV9:PKP2 improves heart function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy. Communications medicine 44 38499690
2011 Expression of plakophilins (PKP1, PKP2, and PKP3) in gastric cancers. Diagnostic pathology 41 21194493
2021 CRISPR/Cas9 library screening uncovered methylated PKP2 as a critical driver of lung cancer radioresistance by stabilizing β-catenin. Oncogene 40 33742119
2013 Identification of a PKP2 gene deletion in a family with arrhythmogenic right ventricular cardiomyopathy. European journal of human genetics : EJHG 35 23486541
2011 Expression of Plakophilins (PKP1, PKP2, and PKP3) in breast cancers. Medical oncology (Northwood, London, England) 34 21947748
2012 Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy. Clinical genetics 32 22889254
2011 PKP2 mutations in sudden death from arrhythmogenic right ventricular cardiomyopathy (ARVC) and sudden unexpected death with negative autopsy (SUDNA). Circulation journal : official journal of the Japanese Circulation Society 32 22019812
2017 The human PKP2/plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts. International journal of cancer 31 29044515
2016 Molecular disturbance underlies to arrhythmogenic cardiomyopathy induced by transgene content, age and exercise in a truncated PKP2 mouse model. Human molecular genetics 28 27412010
2018 Pleiotropic Phenotypes Associated With PKP2 Variants. Frontiers in cardiovascular medicine 27 30619891
2021 Transcriptomic Coupling of PKP2 With Inflammatory and Immune Pathways Endogenous to Adult Cardiac Myocytes. Frontiers in physiology 26 33536940
2023 Structural characterization and anti-inflammatory activity of a novel polysaccharide PKP2-1 from Polygonatum kingianum. Frontiers in nutrition 23 37051130
2014 Stop-gain mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy. PloS one 21 24967631
2016 Brugada Syndrome and PKP2: Evidences and uncertainties. International journal of cardiology 17 27085656
2021 Pathogenic variants in plakophilin-2 gene (PKP2) are associated with better survival in arrhythmogenic right ventricular cardiomyopathy. Journal of applied genetics 11 34191271
2017 Quantitative analysis of PKP2 and neighbouring genes in a patient with arrhythmogenic right ventricular cardiomyopathy caused by heterozygous PKP2 deletion. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 10 28431057
2021 PPM1D accelerates proliferation and metastasis of osteosarcoma by activating PKP2. European review for medical and pharmacological sciences 9 33506895
2018 A novel PKP2 mutation and intrafamilial phenotypic variability in ARVC/D. Medical journal of the Islamic Republic of Iran 9 29977873
2017 Generation of iPSC line from patient with arrhythmogenic right ventricular cardiomyopathy carrying mutations in PKP2 gene. Stem cell research 9 29034900
2020 Generation of human induced pluripotent stem cell line LUMCi027-A and its isogenic gene-corrected line from a patient affected by arrhythmogenic cardiomyopathy and carrying the c.2013delC PKP2 mutation. Stem cell research 8 32485643
2016 Arrhythmogenic Right Ventricular Cardiomyopathy - 4 Swedish families with an associated PKP2 c.2146-1G>C variant. American journal of cardiovascular disease 7 27335691
2016 Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs. BMC genetics 7 27357287
2021 Establishment of an arrhythmogenic right ventricular cardiomyopathy derived iPSC cell line (USFi004-A) carrying a heterozygous mutation in PKP2 (c.1799delA). Stem cell research 5 34034221
2021 Phenotypic Variability of a Pathogenic PKP2 Mutation in an Italian Family Affected by Arrhythmogenic Cardiomyopathy and Juvenile Sudden Death: Considerations From Molecular Autopsy to Sport Restriction. Frontiers in cardiovascular medicine 5 34095246
2015 Novel frame-shift mutation in PKP2 associated with arrhythmogenic right ventricular cardiomyopathy: a case report. BMC medical genetics 5 26701096
2024 PKP2 induced by YAP/TEAD4 promotes malignant progression of gastric cancer. Molecular carcinogenesis 4 38804704
2022 A Novel Homozygous PKP2 Variant in Severe Neonatal Non-compaction and Concomitant Ventricular Septal Defect: A Case Report. Frontiers in pediatrics 4 35059364
2021 Generation of three induced pluripotent stem cell lines, SCVIi003-A, SCVIi004-A, SCVIi005-A, from patients with ARVD/C caused by heterozygous mutations in the PKP2 gene. Stem cell research 4 33743362
2020 Generation of an induced pluripotent stem cell line from the dermal fibroblasts of a patient with arrhythmogenic right ventricular cardiomyopathy carrying a PKP2/c.2489 + 1G > A mutation. Stem cell research 4 32916635
2018 Derivation of human induced pluripotent stem cell line EURACi004-A from skin fibroblasts of a patient with Arrhythmogenic Cardiomyopathy carrying the heterozygous PKP2 mutation c.2569_3018del50. Stem cell research 4 30219716
2018 PKP2 and DSG2 genetic variations in Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy registry patients. Anatolian journal of cardiology 4 30391969
2023 The arrhythmogenic cardiomyopathy phenotype associated with PKP2 c.1211dup variant. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 3 37505369
2020 Clinical and Molecular Data Define a Diagnosis of Arrhythmogenic Cardiomyopathy in a Carrier of a Brugada-Syndrome-Associated PKP2 Mutation. Genes 3 32443836
2026 NSUN6-mediated m5C RNA methylation aggravate osteosarcoma progression through promoting PKP2 mRNA stability and expression. Bone 2 41687845
2025 Computational Modeling of Effects of PKP2 Gene Therapy on Ventricular Conduction Properties in Arrhythmogenic Cardiomyopathy. Circulation. Arrhythmia and electrophysiology 2 40201954
2025 Low expression of miR-7-5p promotes resistance to radiotherapy in lung cancer through direct upregulation of PKP2 expression. Scientific reports 2 40374728
2025 Exercise-induced dysregulation of the adrenergic response in a mouse model of PKP2-arrhythmogenic cardiomyopathy. Heart rhythm 2 40383179
2024 CCRR regulate MYZAP-PKP2-Nav1.5 signaling pathway in atrial fibrillation following myocardial infarction. iScience 2 39507261
2024 Adipocyte-Mediated Electrophysiological Remodeling of PKP-2 Mutant Human Pluripotent Stem Cell-Derived Cardiomyocytes. Biomedicines 2 39595168
2021 CRISPR/Cas9-edited PKP2 knock-out (JMUi001-A-2) and DSG2 knock-out (JMUi001-A-3) iPSC lines as an isogenic human model system for arrhythmogenic cardiomyopathy (ACM). Stem cell research 2 33640690
2018 Sequencing of Linkage Region on Chromosome 12p11 Identifies PKP2 as a Candidate Gene for Left Ventricular Mass in Dominican Families. G3 (Bethesda, Md.) 2 29288195
2025 Gene Therapy Targeting Pkp2 Deficiency Attenuates Cardiac Fibrosis: Insights From Single-Cell Transcriptomics in Pkp2-Knockout Rats. MedComm 1 40979216
2025 Epicardial contributions to fibro-inflammatory signaling in a Pkp2-deficient arrhythmogenic cardiomyopathy model. bioRxiv : the preprint server for biology 1 41279609
2024 Generation of CRISPR/Cas9 edited human induced pluripotent stem cell line carrying the heterozygous p.H695VfsX5 frameshift mutation in the exon 10 of the PKP2 gene. Stem cell research 1 38382214
2023 Generation of two edited iPSCs lines by CRISPR/Cas9 with point mutations in PKP2 gene for arrhythmogenic cardiomyopathy in vitro modeling. Stem cell research 1 37393721
2023 The Novel Variant NP_00454563.2 (p.Glu259Glyfs*77) in Gene PKP2 Associated with Arrhythmogenic Cardiomyopathy in 8 Families from Malaga, Spain. Genes 1 37510372
2023 [Analysis of PKP2 gene variants in a child with Arrhythmogenic right ventricular cardiomyopathy]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 37643967
2021 Generation of human induced pluripotent stem cell line EURACi006-A and its isogenic gene-corrected line EURACi006-A-1 from an arrhythmogenic cardiomyopathy patient carrying the c.1643delG PKP2 mutation. Stem cell research 1 34134068
2026 [Distribution characteristics of PKP2 non-synonymous variations in protein domain and genotype-phenotype relationship in patients with arrhythmogenic right ventricular cardiomyopathy]. Zhonghua xin xue guan bing za zhi 0 41529851
2026 Novel PKP2 compound heterozygous mutations causing neonatal early-onset arrhythmogenic cardiomyopathy: insights into the synergistic pathogenicity of biallelic inactivation. Functional & integrative genomics 0 41535644
2026 Generation of a PKP2 heterozygous knockout pig model of arrhythmogenic cardiomyopathy. Zoological research 0 41603024
2026 Fibroblast growth factor 21 prevents catecholaminergic arrhythmias in a mouse model of PKP2 arrhythmogenic cardiomyopathy. Heart rhythm 0 41759869
2026 Pediatric Stroke Associated With a Rare Pathogenic PKP2 Variant: A Diagnostic Challenge. Cureus 0 41769495
2026 Arrhythmogenic Cardiomyopathy: Exercise and Divergent Phenotypes in a Family With a Pathogenic PKP2 Variant. JACC. Case reports 0 41906570
2026 Disease models and AAV therapies of PKP2-induced arrhythmogenic cardiomyopathy. Molecular therapy. Advances 0 42137277
2026 Epicardial Contributions to Fibro-Inflammatory Signaling in a Pkp2-Deficient Arrhythmogenic Cardiomyopathy Model. Circulation. Heart failure 0 42246055
2025 Arrhythmogenic Cardiomyopathy PKP2-Related: Clinical and Functional Characterization of a Pathogenic Variant Detected in Two Italian Families. Genes 0 40282378
2025 Modelling arrhythmogenic cardiomyopathy fattyfibro pathology with PKP2-deficient epicardial cells derived from human iPSCs. Communications biology 0 41145823
2024 Generation of human induced pluripotent stem cell lines UKJi001-A and UKJi006-A from patients with heterozygous mutation in the PKP2 gene. Stem cell research 0 39332132
2024 Computational Modeling of Effects of PKP2 Gene Therapy on Ventricular Conduction Properties in Arrhythmogenic Cardiomyopathy. bioRxiv : the preprint server for biology 0 39764031

Missed literature

Know a paper Affinage missed for PKP2? Flag it for the maintainers and the community.

No submissions yet.