Affinage

ITPR2

Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 · UniProt Q14571

Length
2701 aa
Mass
308.1 kDa
Annotated
2026-06-10
43 papers in source corpus 19 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITPR2 (IP3R2) encodes an ER-resident, IP3-gated calcium release channel whose IP3-binding core undergoes ligand-induced conformational change upon IP3 binding (PMID:30244130), and whose principal physiological role is to govern ER-to-mitochondria Ca2+ transfer at mitochondria-associated membrane (MAM) contact sites (PMID:24797322, PMID:33526781). By delivering ER Ca2+ to the mitochondrial uniporter MCU, ITPR2 drives mitochondrial Ca2+ accumulation, loss of membrane potential, ROS production, and cellular senescence; loss-of-function escapes oncogene-induced and replicative senescence, and Itpr2 knockout mice show extended lifespan, reduced senescence, and fewer ER-mitochondria contacts (PMID:24797322, PMID:33526781), a cascade tunable by the upstream repressor miR-129 (PMID:38218462). ITPR2 is physically integrated into MAM tethering complexes containing VDAC1, Grp75, MICU1, FMO2, ERp29, and FUNDC1, where these partners control complex assembly, channel stability, and mitochondrial Ca2+ flux across contexts of insulin resistance, cardiac hypertrophy, and Treg dysfunction (PMID:35192817, PMID:40489543, PMID:36302455, PMID:40451326). The same Ca2+-release activity feeds diverse downstream programs: NLRP3/Caspase-1/GSDMD pyroptosis in LPS-challenged cardiomyocytes (PMID:38378646), IP3R2/Bcl-2 complex regulation of pro-apoptotic Ca2+ signaling in B-cell lymphoma (PMID:23681227), and isoform-specific control of cell migration (PMID:27347718). In the nervous system, astrocytic IP3R2 is the primary receptor for GPCR-evoked somatic Ca2+ signals (PMID:25894291), while oligodendrocyte IP3R2 sets Ca2+ homeostasis governing OPC proliferation/differentiation and myelination through a MAPK/ERK-CDK6/cyclin D1 axis (PMID:38476116, PMID:34630045). ITPR2 expression is transcriptionally driven by the clock factor BMAL1 (PMID:39343166). ITPR2 also negatively regulates melanophagy through inter-organelle Ca2+ signaling via the AMPK-ULK1 and TFEB/TRPML1 pathways.

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2013 High

    Established that ITPR2 protein level is a determinant of apoptotic Ca2+ signaling, linking channel abundance to cell-death sensitivity through its interaction with Bcl-2.

    Evidence siRNA knockdown plus xestospongin C inhibition with Ca2+ and apoptosis readouts across DLBCL cell lines

    PMID:23681227

    Open questions at the time
    • Direct biochemical mapping of the IP3R2/Bcl-2 interface not resolved
    • Generality beyond lymphoma not addressed
  2. 2014 High

    Identified ITPR2 as a required driver of ER-to-mitochondria Ca2+ transfer that triggers senescence, defining the ITPR2-MCU axis as a senescence/aging pathway.

    Evidence Loss-of-function genetic screen with siRNA knockdown, live-cell Ca2+ imaging, and mitochondrial membrane potential assays in OIS and replicative senescence models

    PMID:24797322

    Open questions at the time
    • Did not establish whether ITPR2 acts at physical MAM contacts in vivo
    • Upstream regulators of channel activity not defined
  3. 2015 High

    Resolved which IP3R isoform underlies astrocyte Ca2+ signaling, showing IP3R2 is the primary receptor for GPCR-dependent somatic Ca2+ but not for process/endfoot signals.

    Evidence Two-photon Ca2+ imaging in slices and in vivo with Ip3r2-/- mice and GPCR stimulation

    PMID:25894291

    Open questions at the time
    • Identity of the channels mediating process/endfoot Ca2+ signals unresolved
    • Downstream circuit consequences not addressed here
  4. 2018 Low

    Demonstrated at the protein-biochemistry level that the human IP3R2 IP3-binding core binds ligand and changes conformation, providing a molecular basis for gating.

    Evidence Bacterial expression of the IBC domain with CD and intrinsic fluorescence spectroscopy plus bioinformatic residue prediction

    PMID:30244130

    Open questions at the time
    • No mutagenesis or structural validation of predicted binding residues
    • Conformational change not linked to channel gating in cells
  5. 2021 High

    Provided in vivo proof that ITPR2 controls organismal aging by physically maintaining ER-mitochondria contacts, converting the cell-level senescence model into a lifespan phenotype.

    Evidence Itpr2 knockout mice with TEM of MAM contacts, lifespan assays, and forced ER-mitochondria contact experiments in vitro

    PMID:33526781

    Open questions at the time
    • Tissue-specific contributions to lifespan not dissected
    • Mechanism tethering ITPR2 to contact-site formation not defined
  6. 2021 Medium

    Showed IP3R2 Ca2+ signaling regulates the timing of oligodendrocyte differentiation and the type of axons myelinated, with functional consequences for nerve conduction.

    Evidence Conventional and conditional Itpr2 knockout mice with immunohistochemistry and optic nerve compound action potential recordings

    PMID:34630045

    Open questions at the time
    • Molecular pathway from Ca2+ to differentiation timing not specified here
    • Single lab
  7. 2022 Medium

    Placed ITPR2 within a defined MAM multiprotein complex (IP3R2-VDAC1-MICU1) whose assembly is modulated by detyrosinated tubulin to cause mitochondrial Ca2+ overload in insulin resistance.

    Evidence Co-IP of the complex, siRNA knockdown, autophagy inhibitors, and Ca2+ imaging in L-02 cells and mice

    PMID:35192817

    Open questions at the time
    • Stoichiometry and direct vs. bridged interactions not resolved
    • Single lab
  8. 2022 Medium

    Identified BMAL1 as a direct transcriptional driver of ITPR2, linking the circadian clock to ITPR2-dependent secretory Ca2+ signaling in acinar cells.

    Evidence Bmal1 knockout rats with ITPR2/ITPR3 adenoviral rescue and BMAL1 promoter-binding analysis

    PMID:39343166

    Open questions at the time
    • Whether circadian ITPR2 oscillation occurs in other tissues not tested
    • Direct ChIP at the ITPR2 promoter not fully detailed
  9. 2022 Medium

    Connected DPP4/ERp29 signaling to ITPR2 stability, showing ERp29 binds IP3R2 and inhibits its degradation to promote MAM formation and Treg dysfunction.

    Evidence Co-IP of ERp29-IP3R2, IGF-2R blockade, DPP4 enzymatic-site mutation in db/db mice and Treg assays

    PMID:36302455

    Open questions at the time
    • Degradation machinery acting on IP3R2 not identified
    • Single lab
  10. 2024 Medium

    Defined a downstream effector arm of ITPR2 Ca2+ release, coupling it to NLRP3/Caspase-1/GSDMD pyroptosis in cardiomyocytes.

    Evidence siRNA knockdown and xestospongin C inhibition with Ca2+ imaging and pyroptosis markers in vitro and in an LPS rat model

    PMID:38378646

    Open questions at the time
    • Mechanistic link between cytosolic Ca2+ and NLRP3 activation not fully resolved
    • Single lab
  11. 2024 Medium

    Identified the signaling axis (MAPK/ERK-CDK6/cyclin D1) through which ITPR2 Ca2+ homeostasis governs OPC proliferation/differentiation and myelination.

    Evidence Oligodendrocyte-specific conditional Itpr2 KO with transcriptomics, Ca2+ imaging, ERK inhibition, and Ca2+-channel antagonism

    PMID:38476116

    Open questions at the time
    • How compensatory plasma membrane channel upregulation is triggered unknown
    • Single lab
  12. 2024 Medium

    Showed ITPR2-enriched MAMs mediate hypoxia-induced photoreceptor mitochondrial Ca2+ overload and apoptosis, extending the MAM-overload model to retinal disease.

    Evidence siRNA knockdown, TEM of MAMs, ER-mitochondria colocalization, and apoptosis assays with an in vivo subretinal model

    PMID:38851477

    Open questions at the time
    • Upstream sensor coupling hypoxia to IP3R2 enrichment unclear
    • Single lab
  13. 2024 Medium

    Established miR-129 as a direct upstream repressor of ITPR2 that controls the entire ER-to-mitochondria Ca2+-senescence cascade, offering a tunable handle on aging.

    Evidence miR-129 gain/loss of function with Ca2+, ROS, MMP assays and an in vivo bleomycin lung aging model

    PMID:38218462

    Open questions at the time
    • Full luciferase reporter validation not explicit
    • Other miR-129 targets contributing to phenotype not excluded
  14. 2025 Medium

    Added FMO2 as a MAM-localized binding partner of the IP3R2-Grp75-VDAC1 complex that bidirectionally tunes ER-mitochondria Ca2+ transfer in cardiac hypertrophy.

    Evidence MAM-targeted mass spectrometry, Co-IP, FMO2 KO and overexpression mice, AAV9 cardiac overexpression, and a contact-enhancing peptide

    PMID:40489543

    Open questions at the time
    • Whether FMO2 directly contacts IP3R2 vs. via Grp75/VDAC1 not resolved
    • Single lab
  15. 2025 Medium

    Identified FUNDC1 as a direct IP3R2 binding partner that stabilizes the channel against ubiquitin-mediated degradation to control MAM Ca2+ overload in hypertrophy.

    Evidence Co-IP of FUNDC1-IP3R2, FUNDC1 gain/loss of function, and mitochondrial Ca2+/function assays in spontaneously hypertensive rats

    PMID:40451326

    Open questions at the time
    • E3 ligase mediating IP3R2 ubiquitination not identified
    • Single lab
  16. 2025 Medium

    Extended ITPR2 inter-organelle signaling beyond the mitochondrion, showing isoform-specific negative regulation of melanophagy via AMPK-ULK1 and ER-lysosome TFEB/TRPML1 pathways.

    Evidence Isoform-specific siRNA, mitochondrial/lysosomal Ca2+ imaging, lysosomal pH, TFEB translocation, and in vivo zebrafish pigmentation (preprint)

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Direct ER-lysosome contact mechanism not biochemically defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the same ITPR2 channel selectively engages distinct downstream programs (senescence, pyroptosis, myelination, melanophagy) in a tissue-specific manner, and what determines its recruitment and stabilization at specific contact sites.
  • No unifying model of contact-site selection
  • Structural basis of partner-driven channel stabilization unknown
  • Tissue-specific effector specificity unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0005198 structural molecule activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005739 mitochondrion 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 1
Partners
BCL2ERP29ERP44FMO2FUNDC1MCUMICU1VDAC1
Complex memberships
IP3R2-Grp75-VDAC1-FMO2 MAM complexIP3R2-VDAC1-MICU1 MAM complexIP3R2/Bcl-2 complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 ITPR2 mediates calcium release from the endoplasmic reticulum (ER) to the mitochondria during oncogene-induced senescence (OIS) and replicative senescence; mitochondrial calcium accumulation via MCU leads to decreased mitochondrial membrane potential, ROS accumulation, and senescence. Loss-of-function screen identified ITPR2 and MCU as senescence regulators, and loss of either enabled escape from OIS. Loss-of-function genetic screen; siRNA knockdown; live-cell calcium imaging; mitochondrial membrane potential assays Nature communications High 24797322
2021 ITPR2 drives cellular senescence and aging by mediating ER-to-mitochondria calcium transfer; Itpr2 knockout mice display increased lifespan, less senescence, fewer mitochondria-ER contacts, and forced ER-mitochondria contacts in vitro induce premature senescence. Ablation of ITPR2 decreases the number of mitochondria-ER contact sites both in vivo and in vitro. Itpr2 knockout mouse model; transmission electron microscopy of MAM contacts; lifespan assays; in vitro forced ER-mitochondria contact experiments; cellular senescence assays Nature communications High 33526781
2015 In astrocytes, IP3R2 is the primary receptor responsible for GPCR-dependent somatic Ca2+ signals. Ip3r2-/- mice lack somatic Ca2+ fluctuations in astrocytes but retain diverse Ca2+ fluctuations in astrocyte processes and end feet that are preserved and can be increased by GPCR activation and neuromodulatory (startle) responses. Two-photon Ca2+ imaging in brain slices and in vivo; Ip3r2-/- knockout mice; GPCR pharmacological stimulation Nature neuroscience High 25894291
2013 IP3R2 protein levels dictate apoptotic sensitivity to disruption of IP3R/Bcl-2 complexes in diffuse large B-cell lymphoma cells; Bcl-2 suppresses IP3R2 hyperactivity, and disrupting the IP3R2/Bcl-2 complex with TAT-IDP(S) peptide promotes IP3-induced pro-apoptotic Ca2+ signaling. Knocking down IP3R2 reduced TAT-IDP(S)-induced apoptosis and Ca2+ release. siRNA knockdown of IP3R2; pharmacological inhibition with xestospongin C; Ca2+ imaging; apoptosis assays; correlation of IP3R2 protein levels with apoptotic responses across multiple cell lines Cell death & disease High 23681227
2016 ERP44 inhibits lung cancer cell migration primarily via IP3R2; ERP44 overexpression reduces intracellular Ca2+ release through IP3Rs and inhibits cell polarization and pseudopodium protrusion. siRNA knockdown of IP3R2 (but not IP3R1 or IP3R3) markedly inhibited wound healing, establishing IP3R2 as the isoform-specific mediator. siRNA knockdown of IP3R1, IP3R2, IP3R3 (isoform-specific comparison); ERP44 overexpression; Ca2+ imaging; wound-healing migration assay; cell morphology analysis Aging Medium 27347718
2022 PFOS-induced early insulin resistance involves formation of an IP3R2-VDAC1-MICU1 complex at the ER-mitochondria interface. Detyrosinated α-tubulin, which increases in an autophagy-dependent manner, interacts with VDAC1 and enhances assembly of this IP3R2-VDAC1-MICU1 complex, promoting mitochondrial Ca2+ overload. Inhibiting autophagy relieved mitochondrial Ca2+ overload and reversed IR. Co-immunoprecipitation (IP3R2-VDAC1-MICU1 complex); siRNA knockdown; autophagy inhibitors; Ca2+ imaging; in vitro (L-02 cells) and in vivo (C57BL/6J mice) models The Science of the total environment Medium 35192817
2025 FMO2 localizes to MAM structures where it binds IP3R2 as a component of the IP3R2-Grp75-VDAC1 complex, maintaining ER-mitochondria contact and regulating mitochondrial Ca2+ signaling for bioenergetics. Deletion or overexpression of FMO2 bidirectionally modulates pathological cardiac hypertrophy progression, and a synthetic peptide enhancing ER-mitochondria contact promoted Ca2+ transfer and prevented hypertrophy. MAM-targeted mass spectrometry; Co-immunoprecipitation; genetic mouse models (FMO2 KO and overexpression); AAV9-mediated cardiac overexpression; neonatal rat cardiomyocyte culture Circulation Medium 40489543
2024 IP3R2-mediated ER Ca2+ release activates the NLRP3/Caspase-1/GSDMD pyroptosis pathway in cardiomyocytes in response to LPS; siRNA knockdown of IP3R2 or pharmacological inhibition with xestospongin C reversed LPS-induced intracellular Ca2+ release and suppressed pyroptosis. Mutual regulation between ER stress and IP3R2-mediated Ca2+ release amplifies this pathway. siRNA knockdown of IP3R2; pharmacological inhibition (xestospongin C, MCC950); Ca2+ imaging; Western blot for NLRP3/Caspase-1/GSDMD; in vivo rat LPS model Cell death discovery Medium 38378646
2024 Loss of ITPR2 in oligodendrocytes disturbs Ca2+ homeostasis, inhibits myelination, and disrupts OPC proliferation/differentiation via the MAPK/ERK-CDK6/cyclin D1 axis. Itpr2 ablation elevates resting [Ca2+]i in OPCs through compensatory upregulation of plasma membrane calcium channels; antagonists against these channels normalize [Ca2+]i and enhance OPC lineage progression. Oligodendrocyte-specific Itpr2 conditional knockout mice; transcriptome profiling; Ca2+ imaging; MAPK/ERK pathway inhibition; pharmacological antagonism of plasma membrane Ca2+ channels Advanced science Medium 38476116
2021 Itpr2 (IP3R2) deficiency in mice causes a developmental delay in oligodendrocyte differentiation, resulting in an increased percentage of CAII+ type I/II oligodendrocytes that preferentially myelinate small-diameter axons, leading to abnormal compound action potentials in optic nerves. Conventional and conditional Itpr2 knockout mice; immunohistochemistry; electrophysiology (CAP recordings in optic nerves); histological analysis Frontiers in cellular neuroscience Medium 34630045
2024 IP3R2-enriched MAMs are increased in photoreceptors under hypoxia; elevated IP3R2 at MAMs leads to mitochondrial calcium overload and apoptosis. IP3R2 knockdown improved mitochondrial morphology and function by limiting MAM formation and attenuating mitochondrial Ca2+ overload. siRNA knockdown; transmission electron microscopy; ER-mitochondria colocalization; MAM reporter; flow cytometry; in vivo subretinal injection model Experimental eye research Medium 38851477
2022 BMAL1 directly regulates the transcription of ITPR2 (and ITPR3); loss of BMAL1 downregulates ITPR2/3 expression and causes vacuolation, atrophy, and secretory dysfunction in lacrimal and parotid acinar cells. Restoration of ITPR2 and ITPR3 expression in Bmal1-deficient rats alleviated symptoms of secretory dysfunction. Bmal1 knockout rats; ITPR2/ITPR3 rescue experiments (adenoviral re-expression); ChIP or transcriptional analysis of BMAL1 binding to ITPR2/3 promoters; secretion assays The ocular surface Medium 39343166
2024 miR-129 directly represses ITPR2 expression and controls ER-to-mitochondria calcium transfer, mitochondrial membrane potential, ROS, DNA damage, and cellular senescence through the ITPR2-MCU axis. Overexpression of miR-129 delayed bleomycin-induced cellular and lung aging in mice. miRNA target validation (luciferase reporter or direct binding assay implied); miR-129 overexpression and inhibition; Ca2+ imaging; ROS and MMP assays; in vivo bleomycin lung aging model Mechanisms of ageing and development Medium 38218462
2022 DPP4 (nonenzymatic function) activates PKA/SP1 signaling via IGF2R binding, which upregulates ERp29 expression; ERp29 binds IP3R2, inhibiting its degradation and promoting MAM formation and mitochondrial Ca2+ overload in Treg cells, impairing Treg function and driving M1 microglia polarization. Co-immunoprecipitation (ERp29-IP3R2); IGF-2R knockdown/blockade; in vivo db/db mouse model; in vitro Treg assays; DPP4 enzymatic-site mutation Metabolism: clinical and experimental Medium 36302455
2018 The IP3-binding core (IBC) domain of human IP3R2 (residues 224-604) binds IP3 with high affinity and undergoes conformational changes in secondary and tertiary structure upon IP3 binding, as detected by far-CD and intrinsic fluorescence spectroscopy. Key conserved ligand-binding residues identified by bioinformatics include R269, K508, and R511. Molecular cloning and bacterial expression of IBC domain; CD spectroscopy; intrinsic fluorescence spectroscopy; bioinformatics of binding-site residues International journal of biological macromolecules Low 30244130
2020 Knockdown of Tcirg1 decreases IP3R2 expression in osteoclast precursors, reducing intracellular Ca2+ levels and limiting nuclear translocation of NFATc1, thereby inhibiting large osteoclast (>100 µm) generation during RANKL-induced differentiation. Lentiviral shRNA knockdown of Tcirg1 in mouse bone marrow-derived monocytes; NFATc1 nuclear translocation assay; Ca2+ imaging; osteoclast differentiation assay PloS one Low 32790690
2025 FUNDC1 binds directly to IP3R2 at MAMs (confirmed by Co-IP); in cardiac hypertrophy, FUNDC1 binding to IP3R2 regulates MAM-associated Ca2+ overload, inducing mitochondrial dysfunction and pyroptosis. FUNDC1 knockdown promotes IP3R2 ubiquitination and degradation, reducing mitochondrial Ca2+ and protecting against hypertrophy. Co-immunoprecipitation (FUNDC1-IP3R2); siRNA knockdown and overexpression of FUNDC1; spontaneously hypertensive rat model; flow cytometry for mitochondrial Ca2+; mitochondrial function assays Life sciences Medium 40451326
2025 IP3R2 knockdown decreases mitochondrial Ca2+ uptake, augments the ADP/ATP ratio, and activates melanophagy via the AMPK-ULK1 pathway. Simultaneously, IP3R2 silencing increases ER-lysosome proximity, elevates lysosomal Ca2+ levels, reduces lysosomal pH, activates lysosomal TRPML1 channel, and stimulates nuclear translocation of TFEB, transcriptionally upregulating melanophagy genes. IP3R2 (but not IP3R1 or IP3R3) is a negative regulator of melanophagy, confirmed in zebrafish in vivo. siRNA knockdown (isoform-specific: IP3R1, IP3R2, IP3R3 compared); ratiometric live-cell imaging probes for melanophagy; Ca2+ imaging (mitochondrial, lysosomal); TFEB nuclear translocation assay; TRPML1 channel activity; in vivo zebrafish pigmentation model bioRxivpreprint Medium
2025 Loss of astrocytic IP3R2 leads to deficits in maturation of glutamatergic (but not GABAergic) synapses in the mouse visual cortex, accompanied by attenuated visually evoked neuronal activation and impaired behavioral responses to visual threat stimuli. Astrocyte morphological complexity is also diminished in the absence of IP3R2. IP3R2 knockout mouse; histological synapse quantification; electrophysiology (visually evoked responses); behavioral visual threat assay; astrocyte morphology analysis bioRxivpreprint Low
2012 Deletion of IP3R2 (IP3-R(2)-/-) did not alter the progression of dilated cardiomyopathy (DCM) or pressure overload hypertrophy in mouse models, despite increased IP3R2 expression and elevated IP3 levels in both disease states. Cardiac chamber dimensions, electrophysiology, contractility, lung congestion, and mortality were unchanged in DCM-2Tg mice with or without IP3R2. Genetic cross of DCM-2Tg with IP3-R(2)-/- mice; transverse aortic constriction on IP3-R(2)-/- mice; echocardiography; electrophysiology; histopathology Circulation. Heart failure Medium 23258573
2014 IP3R2 conditional knockout mice show no change in behavioral tests including anxiety, depression, motor/sensory function, or spatial memory (Morris water maze), indicating that astrocytic IP3R2-mediated Ca2+ signaling is not a major modulator of these behavioral processes. IP3R2 conditional knockout mouse; battery of behavioral tests (anxiety, depression, motor, sensory, Morris water maze) Frontiers in behavioral neuroscience Medium 25429263

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Ca(2+) signaling in astrocytes from Ip3r2(-/-) mice in brain slices and during startle responses in vivo. Nature neuroscience 393 25894291
2014 Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence. Nature communications 187 24797322
2007 ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. The Lancet. Neurology 170 17827064
2021 Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging. Nature communications 154 33526781
2013 IP3R2 levels dictate the apoptotic sensitivity of diffuse large B-cell lymphoma cells to an IP3R-derived peptide targeting the BH4 domain of Bcl-2. Cell death & disease 97 23681227
2014 Astrocyte IP3R2-dependent Ca(2+) signaling is not a major modulator of neuronal pathways governing behavior. Frontiers in behavioral neuroscience 96 25429263
2015 Disruption of IP₃R2-mediated Ca²⁺ signaling pathway in astrocytes ameliorates neuronal death and brain damage while reducing behavioral deficits after focal ischemic stroke. Cell calcium 62 26433454
2021 Astrocytic IP3Rs: Beyond IP3R2. Frontiers in cellular neuroscience 50 34393726
2022 Nonenzymatic function of DPP4 promotes diabetes-associated cognitive dysfunction through IGF-2R/PKA/SP1/ERp29/IP3R2 pathway-mediated impairment of Treg function and M1 microglia polarization. Metabolism: clinical and experimental 42 36302455
2022 Perfluorooctane sulfonate induces mitochondrial calcium overload and early hepatic insulin resistance via autophagy/detyrosinated alpha-tubulin-regulated IP3R2-VDAC1-MICU1 interaction. The Science of the total environment 34 35192817
2024 IP3R2-mediated Ca2+ release promotes LPS-induced cardiomyocyte pyroptosis via the activation of NLRP3/Caspase-1/GSDMD pathway. Cell death discovery 29 38378646
2015 Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese. Arthritis & rheumatology (Hoboken, N.J.) 28 25303641
2022 Ferulic acid attenuates high glucose-induced MAM alterations via PACS2/IP3R2/FUNDC1/VDAC1 pathway activating proapoptotic proteins and ameliorates cardiomyopathy in diabetic rats. International journal of cardiology 27 36481261
2016 ERP44 inhibits human lung cancer cell migration mainly via IP3R2. Aging 27 27347718
2009 No evidence of association of FLJ10986 and ITPR2 with ALS in a large German cohort. Neurobiology of aging 22 19464757
2012 No contribution of IP3-R(2) to disease phenotype in models of dilated cardiomyopathy or pressure overload hypertrophy. Circulation. Heart failure 17 23258573
2023 Proteomic analysis of ITPR2 as a new therapeutic target for curcumin protection against AFB1-induced pyroptosis. Ecotoxicology and environmental safety 15 37257342
2024 ITPR2 Mediated Calcium Homeostasis in Oligodendrocytes is Essential for Myelination and Involved in Depressive-Like Behavior in Adolescent Mice. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 38476116
2020 Knockdown of Tcirg1 inhibits large-osteoclast generation by down-regulating NFATc1 and IP3R2 expression. PloS one 12 32790690
2025 FMO2 Prevents Pathological Cardiac Hypertrophy by Maintaining the ER-Mitochondria Association Through Interaction With IP3R2-Grp75-VDAC1. Circulation 10 40489543
2021 Evidence That ITPR2-Mediated Intracellular Calcium Release in Oligodendrocytes Regulates the Development of Carbonic Anhydrase II + Type I/II Oligodendrocytes and the Sizes of Myelin Fibers. Frontiers in cellular neuroscience 10 34630045
2020 Minimal contribution of IP3R2 in cardiac differentiation and derived ventricular-like myocytes from human embryonic stem cells. Acta pharmacologica Sinica 9 33037404
2017 Germline genetic variations in PDZD2 and ITPR2 genes are associated with clear cell renal cell carcinoma in Chinese population. Oncotarget 9 26918600
2024 IP3R2 regulates apoptosis by Ca2+ transfer through mitochondria-ER contacts in hypoxic photoreceptor injury. Experimental eye research 8 38851477
2024 BMAL1 deficiency provokes dry mouth and eyes by down-regulating ITPR2/3. The ocular surface 8 39343166
2022 A requirement for astrocyte IP3R2 signaling for whisker experience-dependent depression and homeostatic upregulation in the mouse barrel cortex. Frontiers in cellular neuroscience 8 36090792
2024 Calcium transferring from ER to mitochondria via miR-129/ITPR2 axis controls cellular senescence in vitro and in vivo. Mechanisms of ageing and development 7 38218462
2018 Experimental and theoretical study of IBC domain from human IP3R2; molecular cloning, bacterial expression and protein purification. International journal of biological macromolecules 6 30244130
2025 The IP3R2 Knockout Mice in Behavior: A Blessing or a Curse? Journal of neurochemistry 5 40172184
2020 In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2 Mice Exhibiting Depressive-Like Behavior. Neural plasticity 4 32952549
2025 METTL3-mediated m6A modification of FUNDC1/IP3R2 pathway facilitates cardiac hypertrophy in obesity hypertension. Life sciences 3 40451326
2015 Effects of IP3R2 Receptor Deletion in the Ischemic Mouse Retina. Neurochemical research 3 26446037
2025 Role of IP3R2-Mediated mitochondrial calcium homeostasis in early hypoxic stress injury of retinal pigment epithelial cells. Biochemical and biophysical research communications 2 40267840
2025 IP3R2-Mediated Astrocytic Ca2+ Transients Are Critical to Sustain Modulatory Effects of Locomotion on Neurons in Mouse Somatosensory Cortex. Cells 2 40710356
2019 Genetic variants in the ITPR2 gene are associated with Kashin-Beck Disease in Tibetan. Molecular genetics & genomic medicine 2 31066235
2025 Discovery metabolomics and genetic analysis reveal lipid pathway alterations associated with malignant phenotype acquisition in pleomorphic adenoma and a novel NTF3::ITPR2 fusion in carcinoma ex pleomorphic adenoma. Virchows Archiv : an international journal of pathology 1 41081890
2024 Expression of ITPR2 regulated by lncRNA-NONMMUT020270.2 in LPS-stimulated HT22 cells. Heliyon 1 39040287
2023 Genetic Ablation of Inositol 1,4,5-Trisphosphate Receptor Type 2 (IP3R2) Fails to Modify Disease Progression in a Mouse Model of Spinocerebellar Ataxia Type 3. International journal of molecular sciences 1 37445783
2020 [Changes in three-dimensional arterial spin labeling perfusion imaging of the hippocampus in depressive Itpr-/- mice]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 32376566
2026 ITPR2 Promotes Acute Myeloid Leukemia Progression Through Calcium-Mediated Mitochondrial Dysfunction. Frontiers in bioscience (Landmark edition) 0 41761959
2026 Discovery of a novel ITPR2::KRAS fusion in large cell neuroendocrine lung cancer: a case report. Translational lung cancer research 0 41808705
2026 Validation of ITPR2, DPF3, EPAS1, and PVT1-associated SNPs as biomarkers for RCC in an independent case-control cohort. Frontiers in medicine 0 41889506
2026 Huoxue Qianyang Qutan Recipe limits cardiac remodeling by regulating FUNDC1/IP3R2 signaling pathway in obese hypertensive rats. Scientific reports 0 42243495

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