Affinage

PLN

Phospholamban · UniProt P26678

Length
52 aa
Mass
6.1 kDa
Annotated
2026-06-10
65 papers in source corpus 21 papers cited in narrative 22 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

Phospholamban (PLN) is a small sarcoplasmic reticulum (SR) regulatory protein that tonically inhibits the Ca2+-ATPase SERCA2a, thereby setting the rate of SR Ca2+ re-uptake and cardiac relaxation (PMID:25208486, PMID:12589804). This inhibition is dynamically relieved through multiple post-translational and signaling inputs: PKA-anchored phosphorylation organized by AKAP5 (PMID:35041539), CaMKII-mediated Thr-17 phosphorylation downstream of hypertrophic stimuli (PMID:26930364), PKGIα-dependent phosphorylation promoting relaxation, and direct S-sulfhydration by H2S that modulates lusitropy (PMID:23785074). PLN inhibition of SERCA2a can also be relieved by physical displacement, as shown by acylphosphatase, which competitively reduces PLN co-precipitation with SERCA2a (PMID:12589804), and by FIR-induced dissociation of PLN from SERCA2 in vascular smooth muscle (PMID:41406161). Beyond SERCA2a, PLN binds the anti-apoptotic protein HAX-1, coupling SR Ca2+ handling to cell-survival pathways (PMID:18415121). PLN expression and dosage are themselves disease-relevant: a promoter mutation lowering PLN expression associates with apical hypertrophic cardiomyopathy (PMID:16829191), and a homozygous null variant abolishing PLN protein causes severe recessive dilated cardiomyopathy (PMID:30638982). The R14del variant is a central pathogenic allele: it impairs Ser-16 phosphorylation and alters SERCA2a/HAX-1 binding (PMID:35805951), drives early perinuclear PLN aggregation within disorganized SR before functional deficits appear (PMID:34587756, PMID:37955153), impairs the ER/mitochondria compartment with prolonged Ca2+ decay and oxidative stress (PMID:33998164), and activates a protective unfolded protein response (PMID:33928785). Allele-specific CRISPR disruption and delivery of an interaction-blocking PLN variant (L31A/I40A) each rescue the R14del phenotype, establishing that the aberrant R14del/SERCA2a interaction is causally pathogenic (PMID:35191471, PMID:41545752).

Mechanistic history

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

    Established that PLN inhibition of SERCA2a is reversible by physical displacement, not solely by phosphorylation, defining a competitive-occupancy model of regulation.

    Evidence Reciprocal Co-IP of SERCA2a, PLN, and recombinant acylphosphatase from heart SR vesicles with quantitative displacement

    PMID:12589804

    Open questions at the time
    • Physiological relevance of acylphosphatase as an endogenous displacer in vivo not established
    • Structural basis of displacement not resolved
  2. 2006 Medium

    Showed that PLN expression level itself is disease-relevant, as a promoter mutation reducing transcription associates with hypertrophic cardiomyopathy.

    Evidence Luciferase reporter assays of the -42 C>G promoter variant in C6 and C2C12 cells

    PMID:16829191

    Open questions at the time
    • Causality in patients shown by association, not genetic rescue
    • Mechanism linking reduced PLN to apical hypertrophy not defined
  3. 2008 Medium

    Extended PLN function beyond Ca2+ handling by identifying HAX-1 as a binding partner, linking the SERCA2a/PLN complex to anti-apoptotic survival signaling.

    Evidence Co-immunoprecipitation/pulldown identifying HAX-1 and functional characterization of its anti-apoptotic role

    PMID:18415121

    Open questions at the time
    • Single lab identification
    • Functional consequence of PLN-HAX-1 binding for cell survival not directly dissected
  4. 2013 Medium

    Identified S-sulfhydration as a novel post-translational modification of PLN contributing to impaired relaxation, broadening the regulatory inputs onto PLN.

    Evidence Modified biotin-switch assay and functional measurement in isolated perfused rat hearts

    PMID:23785074

    Open questions at the time
    • Sulfhydration site not mapped
    • Interplay with phosphorylation not addressed
  5. 2014 Medium

    Placed PLN in a force-transduction signaling module by showing ILK regulates SERCA2a and PLN phosphorylation, connecting mechanical signaling to Ca2+ handling.

    Evidence Co-IP, phospho-PLN Western blot, and cardiac function assays in human DCM tissue and mouse models with an ILK R211A gain-of-function mutant

    PMID:25208486

    Open questions at the time
    • Whether ILK acts directly or via an intermediary kinase on PLN unclear
    • Single lab
  6. 2016 Low

    Linked upstream hormonal and hypertrophic signaling to PLN, with TSH suppressing the PKA/PLN pathway and urotensin II driving CaMKII-mediated Thr17 phosphorylation.

    Evidence Neonatal rat cardiomyocyte treatments with SERCA2a activity, phospho-PLN Western blots, and CaMKII inhibition (KN-93)

    PMID:26930364 PMID:27206677

    Open questions at the time
    • Indirect pathway placement without genetic validation of PLN as the causal node
    • Pharmacological inhibition only
  7. 2018 Medium

    Demonstrated that complete loss of PLN protein causes severe recessive dilated cardiomyopathy, with heterozygotes unaffected, establishing the consequences of PLN dosage in humans.

    Evidence Western blot of reduced PLN expression and pedigree segregation of a homozygous p.Glu2Ter variant

    PMID:30638982

    Open questions at the time
    • Mechanism downstream of PLN loss not dissected
    • Single pedigree
  8. 2021 High

    Characterized the cellular pathology of R14del, showing it is initiated by PLN aggregation within disorganized SR and ER/mitochondrial impairment, and that the cell mounts a protective unfolded protein response.

    Evidence Isogenic hiPSC-CMs and time-course R14del mice with proteomics, EM, Ca2+ recording, scRNA-seq, siRNA UPR-branch silencing, and Ca2+-scavenger rescue

    PMID:33928785 PMID:33998164 PMID:34587756

    Open questions at the time
    • Molecular trigger initiating PLN aggregation not defined
    • Whether aggregation or Ca2+ defect is the primary insult unresolved
  9. 2021 Medium

    Surfaced a key controversy by showing R14del produces SERCA2a incompetence (hyperdynamic Ca2+) rather than super-inhibition, contradicting models of enhanced inhibitory binding.

    Evidence Ca2+ transient recording and SERCA2a/PLN immunolabeling in isogenic hiPSC-CMs with a SERCA2a activator probe

    PMID:34948294

    Open questions at the time
    • Discrepancy with super-inhibition models not reconciled
    • Loss of perinuclear co-localization mechanism unexplained
  10. 2022 Medium

    Provided the contrasting biochemical model that R14del enhances binding to SERCA2a, HAX-1, and HRC to super-inhibit Ca2+ affinity while resisting Ser-16 phosphorylation rescue.

    Evidence Co-IP of PLN-R14del with SERCA2a/HAX-1/HRC, phosphorylation Western blots, and in silico structural prediction

    PMID:35805951

    Open questions at the time
    • Directly conflicts with the incompetence model from the same year
    • In silico structural claims not experimentally validated
  11. 2022 High

    Established causality of the R14del allele in vivo by showing allele-specific disruption rescues cardiac function and arrhythmia susceptibility.

    Evidence AAV9-CRISPR/Cas9 allele disruption in humanized mice with cardiac MRI, ex vivo electrophysiology, and amplicon sequencing

    PMID:35191471

    Open questions at the time
    • Does not resolve which downstream defect (aggregation vs Ca2+) is rescued
    • Editing efficiency requirements for clinical translation unknown
  12. 2022 Low

    Defined AKAP5 as the scaffold anchoring PKA to PLN/SERCA2a, organizing the phosphorylation that relieves inhibition and protects against apoptosis.

    Evidence Co-localization, Co-IP, and apoptosis rescue in H9C2 cells with the AKAP-disrupting peptide St-Ht31

    PMID:35041539

    Open questions at the time
    • Pathway placement relies on inhibitory peptide only
    • Direct AKAP5-PLN contact versus PKA-bridged interaction not distinguished
  13. 2023 High

    Identified the perinuclear PLN clusters as disorganized SR and showed DWORF overexpression reduces SR malformation and extends lifespan independent of Ca2+ handling, separating the morphological from the Ca2+ defect.

    Evidence Transgenic mouse crosses with survival analysis, Ca2+ measurements, SR-marker co-localization, and EM in human R14del tissue

    PMID:37955153

    Open questions at the time
    • Mechanism by which DWORF prevents SR malformation unclear
    • Whether SR disorganization is reversible after onset unknown
  14. 2024 Medium

    Reinforced the incompetence model in transgenic mice and linked R14del to depressed, Ca2+-dependent energy metabolism, implicating metabolic stress as an early mechanism.

    Evidence Ca2+ dynamics, O2 consumption, and metabolism assays in ventricular myocytes with pharmacological SERCA2a/PLN comparisons

    PMID:38214033

    Open questions at the time
    • Conflict with super-inhibition biochemistry unresolved
    • Causal link between metabolic stress and contractile failure not established
  15. 2024 Medium

    Extended PLN missense pathology beyond R14del, showing R9C drives stress-dependent sarcomere and autophagy defects with pentamer aggregation that autophagy activation can mitigate.

    Evidence R9C knock-in and patient iPSC-CMs with transcriptomics, Ca2+ imaging, autophagy flux assays, and metformin/rapamycin rescue (preprint)

    PMID:38659742

    Open questions at the time
    • Preprint, not peer-reviewed
    • Generalizability of autophagy rescue to other PLN variants untested
  16. 2025 Medium

    Refined R14del Ca2+ pathology by showing elevated ER Ca2+ loading as a compartment-specific defect, and demonstrated PLN-SERCA2 dissociation drives Ca2+ reuptake in vascular smooth muscle, generalizing the regulatory paradigm.

    Evidence AAV6-CEPIAer ER Ca2+ sensing in isogenic hiPSC-CMs; Co-IP of FIR-induced PLN/SERCA2 dissociation with knockdown and aortic contraction assays

    PMID:40791987 PMID:41406161

    Open questions at the time
    • Relationship between elevated ER load and cytosolic incompetence not integrated
    • FIR mechanism of dissociation at molecular level undefined
  17. 2026 High

    Provided proof-of-concept therapy by showing an interaction-blocking PLN variant (L31A/I40A) rescues R14del pathology in mice and human cardiomyocytes, establishing the aberrant R14del/SERCA2a interaction as a tractable target.

    Evidence AAV-delivered PLN-L31A/I40A in CRISPR R14del mice and hESC-CMs with echocardiography, histology, and contractile assays

    PMID:41545752

    Open questions at the time
    • Does not reconcile super-inhibition versus incompetence models
    • Long-term durability and dosing not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved whether PLN-R14del acts primarily through SERCA2a super-inhibition or loss of inhibitory competence, and how SR disorganization, ER Ca2+ overload, metabolic stress, and protein aggregation are causally ordered.
  • Conflicting biochemical and functional models from comparable systems
  • No structural model of the R14del/SERCA2a/HAX-1 assembly
  • Primary initiating lesion versus secondary adaptations not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140313 molecular sequestering activity 3
Localization
GO:0005783 endoplasmic reticulum 2
Partners
AKAP5ATP2A2HAX1HRCILKPRKACA
Complex memberships
SERCA2a-PLN complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Phospholamban (PLN) inhibits SERCA2a, and integrin-linked kinase (ILK) mediates cardiomyocyte force transduction through regulation of SERCA2a and phosphorylation of PLN; a synthetic ILK point mutation (ILK R211A) enhances cardiac function through the SERCA2a/PLN module. Co-immunoprecipitation, Western blot for PLN phosphorylation, cardiac function assays in human DCM samples and mouse models Nature communications Medium 25208486
2008 PLN interacts with HS-1-associated protein X-1 (HAX-1), an anti-apoptotic protein with similarities to Bcl-2, linking Ca2+ homeostasis regulated by the SERCA2a/PLN complex to cell survival pathways. Co-immunoprecipitation/pulldown identifying HAX-1 as a PLN-binding partner; functional characterization of HAX-1 anti-apoptotic role Pflugers Archiv : European journal of physiology Medium 18415121
2022 The PLN R14del mutation causes enhanced binding to SERCA2a and HAX-1 compared to wild-type PLN, resulting in super-inhibition of SERCA2a Ca2+-affinity. Additionally, HRC binding to SERCA2a is increased, inhibiting SERCA2a maximal velocity. Unlike wild-type PLN, phosphorylation at Ser-16 does not occur in PLN-R14del and thus does not relieve SERCA2a inhibition. Co-immunoprecipitation of PLN-R14del with SERCA2a, HAX-1, and HRC; phosphorylation analysis by Western blot; in silico structural predictions International journal of molecular sciences Medium 35805951
2021 PLN R14del mutation causes impairment of the ER/mitochondria compartment in cardiomyocytes, manifesting as prolonged Ca2+ transient decay, lower force, fewer ER/ribosomal/mitochondrial proteins by proteomics, dilated ER, and perinuclear ER protein aggregates with oxidative stress. Ca2+-scavenging (GCaMP6f or parvalbumin) improved the disease phenotype, implicating impaired local Ca2+ cycling. hiPSC-CMs with CRISPR/Cas9 isogenic controls; Ca2+ transient recording; proteomics; electron microscopy; transduction with Ca2+-binding proteins EMBO molecular medicine High 33998164
2021 PLN R14del cardiomyopathy activates the unfolded protein response (UPR); silencing each of the three UPR branches (IRE1, ATF6, or PERK) exacerbated contractile dysfunction in PLN R14del hiPSC-CMs, indicating a protective role for UPR. Activation of UPR with BiP inducer X ameliorated contractility deficit. Single-cell RNA sequencing of hiPSC-CMs; siRNA silencing of UPR branches; 2D and 3D contractility assays; validated in patient heart tissue Circulation High 33928785
2021 PLN protein aggregation is among the earliest manifestations of PLN-R14del cardiomyopathy, appearing before onset of functional deficits at 3 weeks of age; altered protein homeostasis (proteostasis) pathways are activated exclusively in PLN-R14del mice even before disease onset. Echocardiography, ECG, histology, RNA sequencing and mass spectrometry at 3, 5, and 8 weeks in PLN-R14del mice Circulation. Heart failure Medium 34587756
2023 DWORF overexpression in PLN-R14del mice delayed the appearance and formation of large pathogenic perinuclear PLN clusters (identified as disorganized sarcoplasmic/endoplasmic reticulum, not amorphous aggregates) and extended lifespan >2-fold; DWORF did not further accelerate SR Ca2+ reuptake in R14del cardiomyocytes (already enhanced), indicating its benefit is through reducing SR malformation rather than Ca2+ handling. Transgenic mouse crosses, echocardiography, survival analysis, isolated cardiomyocyte Ca2+ measurements, immunofluorescence co-localization with SR markers, electron microscopy in human PLN-R14del heart tissue Circulation research High 37955153
2013 Hydrogen sulfide (H2S) causes S-sulfhydration of phospholamban in the rat heart, contributing to negative lusitropism (impaired relaxation); H2S effects involve the Akt/eNOS/cGMP/PKG pathway and KATP channels. Isolated perfused working and Langendorff rat hearts; Western blot; modified biotin switch (S-sulfhydration) assay American journal of physiology. Regulatory, integrative and comparative physiology Medium 23785074
2003 Acylphosphatase displaces PLN from its interaction with SERCA2a: co-immunoprecipitation experiments showed that adding recombinant acylphosphatase to solubilized heart SR vesicles reduced the amount of PLN co-precipitated with SERCA2a in proportion to acylphosphatase concentration, suggesting competitive displacement of PLN. Co-immunoprecipitation of SERCA2a, PLN, and recombinant acylphosphatase from heart SR vesicles with anti-SERCA2a, anti-PLN, and anti-acylphosphatase antibodies Biochemical and biophysical research communications Medium 12589804
2016 TSH inhibits SERCA2a activity and expression in cardiomyocytes by binding to TSH receptors and inhibiting the PKA/PLN signaling pathway, leading to impaired Ca2+ handling and cardiac dysfunction. Neonatal rat cardiomyocytes treated with TSH; SERCA2a activity assay; Western blot for PLN phosphorylation Oncotarget Low 27206677
2016 Urotensin II induces cardiomyocyte hypertrophy through CaMKII-mediated phosphorylation of PLN at Thr17, which upregulates SERCA2a levels; inhibition of CaMKII with KN-93 reversed PLN Thr17 phosphorylation and hypertrophic responses. Primary neonatal rat cardiomyocytes; Western blot for phospho-CaMKII, phospho-PLN (Thr17), SERCA2a; CaMKII inhibitor KN-93; cell size and Ca2+ measurements Gene Low 26930364
2022 AKAP5 co-localizes and physically interacts with PLN and PKA, anchoring PKA to mediate PLN/SERCA2a signaling; AKAP5 overexpression reduced hypoxia/reoxygenation-induced cardiomyocyte apoptosis via activation of PLN/SERCA2a pathway, and this effect was blocked by the AKAP-disrupting peptide St-Ht31. Immunofluorescence co-localization; co-immunoprecipitation; flow cytometry apoptosis assay; Western blot for phospho-PLN and SERCA2a in H9C2 cells Biochemistry and cell biology Low 35041539
2006 The PLN -42 C>G promoter mutation decreased phospholamban promoter activity by 43–47% in reporter assays, and is associated with reduced PLN expression in apical hypertrophic cardiomyopathy. Luciferase reporter plasmid transient transfection assay in C6 and C2C12 cell lines European journal of heart failure Medium 16829191
2018 A homozygous nonsense PLN variant (p.Glu2Ter) significantly reduced phospholamban protein expression by Western blot, causing severe dilated cardiomyopathy in autosomal recessive inheritance; heterozygous carriers had normal cardiac function, indicating haploinsufficiency is insufficient for disease in this pedigree. Western blot showing reduced PLN expression; next-generation sequencing and Sanger sequencing; pedigree analysis International journal of cardiology Medium 30638982
2022 AAV9-CRISPR/Cas9-mediated disruption of the hPLN-R14del allele in humanized mice improved cardiac function (reduced end-diastolic and stroke volumes) and reduced susceptibility to ventricular tachycardia, demonstrating that the R14del allele is causally responsible for the arrhythmogenic phenotype. In vivo AAV9-CRISPR/Cas9 gene editing; cardiac MRI; ex vivo electrophysiology with isoproterenol/rapid pacing; droplet digital PCR and NGS amplicon sequencing Cardiovascular research High 35191471
2025 FIR irradiation activates SERCA2 in vascular smooth muscle cells by promoting dissociation of PLN from SERCA2, leading to increased Ca2+ reuptake into the SER, reduced cytosolic Ca2+, and decreased MLC phosphorylation and vascular contraction. Co-immunoprecipitation of SERCA2 and PLN before/after FIR treatment; SERCA2 knockdown; thapsigargin inhibition; Ca2+ flux measurement; MLC phosphorylation Western blot; isolated rat aorta contraction assay PloS one Medium 41406161
2024 PLN R14del mutation causes loss (not gain) of SERCA2a inhibition, resulting in hyperdynamic Ca2+ handling consistent with PLN incompetence rather than SERCA2a super-inhibition; energy metabolism is depressed and its dependency on Ca2+ is enhanced, pointing to metabolic stress as an early pathogenetic mechanism. Ca2+ dynamics, O2 consumption, energy metabolism measurements in ventricular myocytes from transgenic mice at 8-12 weeks; pharmacological SERCA2a blockade and PLN antagonism comparisons; transcript and protein analysis Acta physiologica (Oxford, England) Medium 38214033
2021 PLN p.Arg14del mutation leads to loss of perinuclear SERCA2a-PLN co-localization in hiPSC-CMs and results in Ca2+ dynamics compatible with SERCA2a incompetence (not super-inhibition), with faster Ca2+ transient decay and rate-independent time-to-peak; SERCA2a activator PST3093 had minimal effect on mutant cells. Ca2+ transient recording at 36°C in field-stimulated hiPSC-CM clusters; immunolabeling of SERCA2a and PLN; isogenic WT/MUT comparison; pharmacological SERCA2a activator treatment International journal of molecular sciences Medium 34948294
2025 PLN R14del cardiomyopathy is associated with higher ER calcium loading in hiPSC-CMs compared to isogenic controls, as measured by AAV6-encoded ER calcium sensor CEPIAer, suggesting altered ER Ca2+ loading as a disease mechanism distinct from cytosolic Ca2+ dysregulation. AAV6-CEPIAer (ER calcium sensor) in engineered heart tissues and FACS of dissociated cardiomyocytes from isogenic hiPSC-CM lines Frontiers in cell and developmental biology Medium 40791987
2026 AAV delivery of PLN-L31A/I40A (a PLN variant that blocks PLN-R14del interaction with SERCA2a without blocking SERCA2a function) rescued ventricular dilation, cardiac fibrosis, PLN aggregation, and premature death in PLN-R14del mice and improved cardiomyocyte function in human hESC-derived cardiomyocytes, demonstrating that aberrant PLN-R14del/SERCA2a interaction is a pathogenic mechanism. CRISPR-Cas9 generated PLN-R14del mouse model and hESC lines; AAV-mediated PLN-L31A/I40A delivery; echocardiography; histology; Ca2+ and contractile function assays in human cardiomyocytes Acta pharmacologica Sinica High 41545752
2024 PLN R9C mutation causes mild hyperdynamic Ca2+ cycling and increased contractility at baseline; under functional stress (maturation medium), PLN R9C iPSC-CMs exhibit sarcomere disarrangement, Ca2+ handling deficiency, disrupted adrenergic signaling, elevated ROS, interrupted autophagic flux, and increased pentamer PLN aggregation. Autophagy activation with metformin or rapamycin restored autophagic flux, mitigated sarcomere disarrangement, and partially rescued β-adrenergic signaling. PLN R9C knock-in and patient-specific iPSC-CMs; transcriptomic analysis; Ca2+ imaging; contractility assays; ROS measurement; autophagy flux assay; pharmacological rescue with metformin/rapamycin bioRxivpreprint Medium 38659742
2025 PKGIα-dependent phosphorylation of PLN promotes cardiac relaxation; urolithin A activates PKGIα via C42 oxidation, leading to PLN phosphorylation in isolated cardiomyocytes and reversal of diastolic dysfunction in a HFpEF mouse model. Recombinant PKGIα activation assay; Western blot for phospho-PLN in NRVMs; C42S PKGIα knock-in mice; echocardiography; human engineered heart tissue contractility bioRxivpreprint Medium

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Simultaneous delivery of doxorubicin and GG918 (Elacridar) by new polymer-lipid hybrid nanoparticles (PLN) for enhanced treatment of multidrug-resistant breast cancer. Journal of controlled release : official journal of the Controlled Release Society 149 17097178
2009 An overview of the mosaic bacteriocin pln loci from Lactobacillus plantarum. Peptides 117 19465075
2016 Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM. Arteriosclerosis, thrombosis, and vascular biology 82 27470516
2006 In vivo evaluation of a new polymer-lipid hybrid nanoparticle (PLN) formulation of doxorubicin in a murine solid tumor model. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 76 17156986
2021 Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy. Circulation 65 33928785
2011 PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing. American heart journal 57 21167350
2021 Impairment of the ER/mitochondria compartment in human cardiomyocytes with PLN p.Arg14del mutation. EMBO molecular medicine 54 33998164
2014 Anti-Candida activity of two-peptide bacteriocins, plantaricins (Pln E/F and J/K) and their mode of action. Fungal biology 53 24528647
2022 Gene editing reverses arrhythmia susceptibility in humanized PLN-R14del mice: modelling a European cardiomyopathy with global impact. Cardiovascular research 50 35191471
2014 Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function. Nature communications 47 25208486
2003 Inducible bacteriocin production in Lactobacillus is regulated by differential expression of the pln operons and by two antagonizing response regulators, the activity of which is enhanced upon phosphorylation. Molecular microbiology 47 12519198
2006 Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN -42 C>G mutation. European journal of heart failure 44 16829191
2020 Protective effects of P2X7R antagonist in sepsis-induced acute lung injury in mice via regulation of circ_0001679 and circ_0001212 and downstream Pln, Cdh2, and Nprl3 expression. The journal of gene medicine 39 32783373
2008 The role of SERCA2a/PLN complex, Ca(2+) homeostasis, and anti-apoptotic proteins in determining cell fate. Pflugers Archiv : European journal of physiology 36 18415121
1984 Construction and properties of plasmid pKC30, a pBR322 derivative containing the pL-N region of phage lambda. Gene 32 6098529
2021 Protein Aggregation Is an Early Manifestation of Phospholamban p.(Arg14del)-Related Cardiomyopathy: Development of PLN-R14del-Related Cardiomyopathy. Circulation. Heart failure 30 34587756
2009 Genetic diversity of the pln locus among oenological Lactobacillus plantarum strains. International journal of food microbiology 28 19604592
1992 Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in murine popliteal lymph node (PLN) test. Journal of autoimmunity 28 1352686
2022 Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition, Driving Impaired Ca2+ Handling and Arrhythmogenesis. International journal of molecular sciences 27 35805951
2021 Characterization of the PLN p.Arg14del Mutation in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. International journal of molecular sciences 27 34948294
2013 Akt/eNOS signaling and PLN S-sulfhydration are involved in H₂S-dependent cardiac effects in frog and rat. American journal of physiology. Regulatory, integrative and comparative physiology 26 23785074
2014 Inhibitory effect of plantaricin peptides (Pln E/F and J/K) against Escherichia coli. World journal of microbiology & biotechnology 25 25138074
2024 Reassessing the Mechanisms of PLN-R14del Cardiomyopathy: From Calcium Dysregulation to S/ER Malformation. JACC. Basic to translational science 23 39297138
2015 A study in Polish patients with cardiomyopathy emphasizes pathogenicity of phospholamban (PLN) mutations at amino acid position 9 and low penetrance of heterozygous null PLN mutations. BMC medical genetics 23 25928149
2019 High glucose induced calcium overload via impairment of SERCA/PLN pathway and mitochondrial dysfunction leads to oxidative stress in H9c2 cells and amelioration with ferulic acid. Fundamental & clinical pharmacology 22 30739350
2013 The genetics of dilated cardiomyopathy: a prioritized candidate gene study of LMNA, TNNT2, TCAP, and PLN. Clinical cardiology 22 24037902
2023 DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters. Circulation research 21 37955153
2023 Exercise does not influence development of phenotype in PLN p.(Arg14del) cardiomyopathy. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 20 37474840
2003 Genetic and biochemical interactions between the Arp2/3 complex, Cmd1p, casein kinase II, and Tub4p in yeast. FEMS yeast research 20 14554195
1995 In vivo immunosuppressive effects of recombinant ovine interferon-tau (trophoblastin): r.oTP (r.oIFN-tau) inhibits local GVH reaction in mice (PLN assay), prevents fetal resorptions, and favors embryo survival and implantation in the CBA/J x DBA/2 mice combination. American journal of reproductive immunology (New York, N.Y. : 1989) 17 7546244
2018 A PLN nonsense variant causes severe dilated cardiomyopathy in a novel autosomal recessive inheritance mode. International journal of cardiology 16 30638982
2024 Early consequences of the phospholamban mutation PLN-R14del+/- in a transgenic mouse model. Acta physiologica (Oxford, England) 14 38214033
2016 Urotensin II induction of neonatal cardiomyocyte hypertrophy involves the CaMKII/PLN/SERCA 2a signaling pathway. Gene 13 26930364
2016 TSH inhibits SERCA2a and the PKA/PLN pathway in rat cardiomyocytes. Oncotarget 13 27206677
2007 Popliteal lymph node (PLN) assay to study adjuvant effects on respiratory allergy. Methods (San Diego, Calif.) 13 17161303
2022 Ranolazine rescues the heart failure phenotype of PLN-deficient human pluripotent stem cell-derived cardiomyocytes. Stem cell reports 10 35334215
2019 Genetic Variation of pln Loci Among Probiotic Lactobacillus plantarum Group Strains with Antioxidant and Cholesterol-Lowering Ability. Probiotics and antimicrobial proteins 10 29027118
2022 Exploring the Correlation Between Fibrosis Biomarkers and Clinical Disease Severity in PLN p.Arg14del Patients. Frontiers in cardiovascular medicine 9 35097021
2020 Femtosecond Plasmonic Laser Nanosurgery (fs-PLN) mediated by molecularly targeted gold nanospheres at ultra-low pulse fluences. Scientific reports 9 32709944
2003 Acylphosphatase interferes with SERCA2a-PLN association. Biochemical and biophysical research communications 9 12589804
1994 Lymphocyte activation by liposome-trapped streptozotocin in murine popliteal lymph node (PLN) test. International journal of immunopharmacology 8 7843853
2022 A-kinase anchoring protein 5 anchors protein kinase A to mediate PLN/SERCA to reduce cardiomyocyte apoptosis induced by hypoxia and reoxygenation. Biochemistry and cell biology = Biochimie et biologie cellulaire 6 35041539
2022 Generation of human induced pluripotent stem cell (iPSC) lines derived from five patients carrying the pathogenic phospholamban-R14del (PLN-R14del) variant and three non-carrier family members. Stem cell research 6 35247838
1995 Different T-cell activation by streptozotocin and Freund's adjuvant in popliteal lymph node (PLN). International journal of immunopharmacology 6 7558513
1995 Immunoactivating potential of multilamellar liposome vesicles (MLV) in murine popliteal lymph node (PLN) test. International journal of immunopharmacology 6 7591360
2023 Generation and characterization of novel human induced pluripotent stem cell (iPSC) lines originating from five asymptomatic individuals carrying the PLN-R14del pathogenic variant and a non-carrier relative. Stem cell research 5 37748331
2020 Incorporating the Number of PLN into the AJCC Stage Could Better Predict the Survival for Patients with NSCLC: A Large Population-Based Study. Journal of oncology 5 33381175
2025 Additional genetic variants in cardiomyopathy patients with the pathogenic PLN p.(Arg14del) founder variant. International journal of cardiology 4 40222661
2023 Phenotypic and Genetic Factors Associated with Absence of Cardiomyopathy Symptoms in PLN:c.40_42delAGA Carriers. Journal of cardiovascular translational research 4 36622581
2022 Generation of human induced pluripotent stem cell lines carrying heterozygous PLN mutation from dilated cardiomyopathy patients. Stem cell research 4 35853412
2025 Identification of disease-specific pathways and modifiers in phospholamban R14del cardiomyopathy: rationale, design and baseline characteristics of DECIPHER-PLN cohort. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 2 40048085
2025 Altered endoplasmic reticulum calcium loading in human PLN-R14del cardiomyopathy. Frontiers in cell and developmental biology 2 40791987
2025 The SERCA-PLN-DWORF axis in cardiometabolic disease: mechanisms and therapeutic perspectives. Cardiovascular diabetology 2 41390717
2018 Insertional Mutagenesis Confounds the Mechanism of the Morbid Phenotype of a PLNR9C Transgenic Mouse Line. Journal of cardiac failure 2 29325795
1997 The alloreactivity in the popliteal lymph node (PLN) assay is regulated by malononitrilamides (MNAs). International journal of tissue reactions 2 9506317
2026 PLN-L31A/I40A for the treatment of inherited heart disease caused by PLN-R14del mutations. Acta pharmacologica Sinica 1 41545752
2024 Deletion of DWORF does not affect cardiac function in aging and in PLN-R14del cardiomyopathy. American journal of physiology. Heart and circulatory physiology 1 38334971
2024 Mitigation of Stress-induced Structural Remodeling and Functional Deficiency in iPSC-CMs with PLN R9C Mutation by Promoting Autophagy. bioRxiv : the preprint server for biology 1 38659742
2024 Safety evaluation of a food enzyme with phospholipase A1 and lysophospholipase activities from the genetically modified Aspergillus niger strain PLN. EFSA journal. European Food Safety Authority 1 38711806
2024 From Ca2+ dysregulation to heart failure: β-adrenoceptor activation by RKIP postpones molecular damages and subsequent cardiac dysfunction in mice carrying mutant PLNR9C by correction of aberrant Ca2+-handling. Pharmacological research 1 39742932
2026 Hypertrophic cardiomyopathy associate with a PLN gene mutation in a child: a case report. AME case reports 0 41971917
2025 The PLN Foundation is striving for a cure, but who owns the disease? Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 0 40338481
2025 Cardiac remodeling pathways do not accelerate disease onset and severity in a mouse model of PLN-R14del cardiomyopathy. Scientific reports 0 41068173
2025 Generation and characterization of human induced pluripotent stem cell (iPSC) lines from two asymptomatic Greek carriers of the Phospholamban (PLN)-R14del pathogenic variant and a non-carrier relative. Stem cell research 0 41176972
2025 Far-infrared irradiation attenuates vessel contraction by activating SERCA2 through disruption of SERCA2 and PLN interaction. PloS one 0 41406161

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