Affinage

NPRL2

GATOR1 complex protein NPRL2 · UniProt Q8WTW4

Length
380 aa
Mass
43.7 kDa
Annotated
2026-06-10
49 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NPRL2 is the catalytic subunit of the lysosomal GATOR1 complex, where it functions as the GTPase-activating protein that couples amino acid availability to mTORC1 signaling (PMID:30651352, PMID:24786828). It provides the catalytic arginine finger (Arg-78) that stimulates GTP hydrolysis by RagA, and mutation of this residue renders mTORC1 insensitive to amino acid starvation (PMID:30651352); in concert with its partner Nprl3 it localizes to lysosomes and autolysosomes and restrains TORC1 during nutrient scarcity, cooperating with the Tsc1/2 axis (PMID:24786828). NPRL2 toggles between Raptor binding in amino acid sufficiency and Rag GTPase binding in scarcity, implementing a reciprocal 'seesaw' control of mTORC1 (PMID:26582740). In vivo, loss of NPRL2 elevates mTORC1 signaling and produces neuronal hypertrophy, altered excitatory/inhibitory balance, sodium channel (Scn1A) upregulation, and spontaneous seizures, phenotypes rescued by rapamycin (PMID:35165201, PMID:35602938, PMID:34965576). Beyond nutrient sensing, NPRL2 is required for lysosomal acidification and cobalamin-dependent methionine synthesis (PMID:26166573). Its own abundance is set by ubiquitin-proteasome control: HSP70 directs CHIP-mediated polyubiquitination and degradation of NPRL2, while UBE2M binding stabilizes it (PMID:39495541, PMID:33905671). NPRL2 additionally engages the DNA damage response, restoring checkpoint signaling through the ATM–CHK1/2–CDC25 axis (PMID:20700484) and, upon radiation, translocating to the nucleus via AMPK-mediated WDR24 phosphorylation to directly inhibit the E3 ligases HERC2 and RNF8 and protect DNA repair proteins (PMID:41584340). Functional links to PDK1 inhibition (PMID:18616680) and HERC2-dependent BRCA1 stabilization (PMID:25480944) further extend its regulatory reach.

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2004 Low

    Established NPRL2 as a candidate tumor suppressor and defined its domain architecture, framing it as a multidomain nuclear/protein-binding protein before any mechanism was known.

    Evidence Sequence analysis and tet-controlled re-expression with SCID mouse tumor suppression assay

    PMID:15374952

    Open questions at the time
    • Domain assignments are computational, not structurally validated
    • No molecular mechanism for tumor suppression defined
    • MutS-core similarity has no demonstrated biochemical function
  2. 2008 Medium

    Provided an early biochemical activity by showing NPRL2 binds PDK1 and suppresses its Src-dependent activation, the first defined protein-protein mechanism.

    Evidence Two-hybrid screen, co-IP, in vitro kinase assay, and deletion mutagenesis in cells

    PMID:18616680

    Open questions at the time
    • Single lab without reciprocal in vivo validation
    • Relationship to GATOR1/mTORC1 role unclear
    • Physiological context of PDK1 inhibition not defined
  3. 2010 Medium

    Connected NPRL2 to the DNA damage response and revealed conserved proteasomal control of the protein via the yeast ortholog.

    Evidence NPRL2 re-expression in cisplatin-resistant NSCLC with checkpoint marker analysis and xenografts; yeast Npr2 SCF(Grr1) phosphodegron genetics and proteasome inhibition

    PMID:20154027 PMID:20700484

    Open questions at the time
    • Whether ATM-CHK1/2 activation is direct or downstream of altered signaling is unresolved
    • Casein-kinase phosphodegron not mapped onto human NPRL2
    • Connection between checkpoint role and nutrient sensing not established
  4. 2014 High

    Defined NPRL2 as a lysosome-localized TORC1 inhibitor acting with Nprl3 and Tsc1/2, and separately as an HERC2-binding stabilizer of BRCA1, establishing both its nutrient-sensing and genome-maintenance arms.

    Evidence Drosophila co-IP, immunofluorescence, genetic epistasis with Tsc1/2; human co-IP, ubiquitination and HR repair assays

    PMID:24786828 PMID:25480944

    Open questions at the time
    • Mechanism by which NPRL2 prevents HERC2-mediated BRCA1 ubiquitination not biochemically reconstituted
    • Quantitative contribution of Nprl2/3 versus Tsc1/2 to TORC1 control unclear
  5. 2015 Medium

    Built the molecular logic of mTORC1 control by showing NPRL2 binds Raptor in nutrient sufficiency and Rag GTPases in scarcity, and demonstrated NPRL2 is required for lysosomal cobalamin/methionine metabolism in vivo.

    Evidence Co-IP with Rag mutants and Drosophila genetics; conditional KO mouse, metabolomics, and cyanocobalamin rescue

    PMID:26166573 PMID:26582740

    Open questions at the time
    • Structural basis of the Raptor/Rag binding switch not resolved
    • Mechanism linking NPRL2 to lysosomal acidification and transcobalamin 2 processing undefined
    • Whether cobalamin defect is GATOR1-dependent unclear
  6. 2017 Medium

    Showed that supraphysiological NPRL2 drives ROS-dependent DNA damage and checkpoint-mediated arrest, with outcomes branching on p53 status.

    Evidence Overexpression with ROS assay, nuclear co-localization with AIF, and cell cycle analysis

    PMID:29127423

    Open questions at the time
    • Overexpression system may not reflect endogenous function
    • How NOX2/ROS induction connects to GATOR1 role unknown
    • Nuclear AIF co-localization mechanism not defined
  7. 2019 High

    Pinpointed Arg-78 as the catalytic arginine finger driving GATOR1 GAP activity toward RagA, defining the precise enzymatic basis of NPRL2-dependent mTORC1 inhibition.

    Evidence Site-directed mutagenesis, in vitro GTP hydrolysis assay, co-IP, and structural analysis

    PMID:30651352

    Open questions at the time
    • Regulation of GAP activity by upstream signals not addressed
    • Does not connect catalytic mechanism to non-mTORC1 functions
  8. 2022 Medium

    Established the in vivo consequences of NPRL2 loss in neurons as mTORC1-driven, linking it to seizures, neuronal hypertrophy, synaptic imbalance, and neurotransmitter metabolism.

    Evidence Conditional neuronal/neocortical KO mice with electrophysiology, metabolomics, EEG, and rapamycin rescue

    PMID:34965576 PMID:35165201 PMID:35602938

    Open questions at the time
    • Rapamycin does not rescue cell enlargement, indicating mTORC1-independent effects
    • Mechanism linking NPRL2 loss to glycine elevation and Scn1A upregulation incomplete
    • Single-lineage conditional models limit generalization
  9. 2024 Medium

    Defined opposing ubiquitin-system inputs that set NPRL2 abundance—HSP70/CHIP-driven degradation versus UBE2M-mediated stabilization—and extended NPRL2 into tumor immune regulation.

    Evidence Co-IP, ubiquitination assays, HSP70 and UBE2M manipulation, mTORC1 and autophagy flux readouts; TRIM16/Gal-3 cuproptosis assays in glioma

    PMID:33905671 PMID:39367988 PMID:39495541

    Open questions at the time
    • Degradation and stabilization pathways not reconciled into a single regulatory model
    • ERK1/2–TRIM16–Gal-3 axis is correlative regarding direct NPRL2 enzymatic involvement
    • Single-lab findings without independent replication
  10. 2025 Medium

    Revealed a signal-induced relocalization mechanism whereby radiation triggers AMPK/WDR24-dependent nuclear translocation of NPRL2 to directly inhibit HERC2 and RNF8 and confer radioresistance.

    Evidence Nuclear fractionation, domain-binding assays to E3 ligase catalytic domains, AMPK inhibition, and radiosensitivity assays in vitro and in vivo

    PMID:41584340

    Open questions at the time
    • How NPRL2 dissociates from GATOR1 mechanistically not fully defined
    • Stoichiometry of nuclear versus lysosomal pools unknown
    • Single-lab study
  11. 2026 Medium

    Extended NPRL2 to antiviral defense by showing it mediates K63-linked ubiquitination of PRRSV Nsp1α to drive its autophagic degradation.

    Evidence Co-IP, K63-linkage-specific ubiquitination assay, LC3-II autophagy flux, viral replication assay, and domain mapping

    PMID:41742785

    Open questions at the time
    • Whether NPRL2 acts as an E3 ligase or adaptor in this ubiquitination is undefined
    • Relationship to GATOR1/autophagy regulation unclear
    • Single-lab, single-virus context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NPRL2's distinct activities—GATOR1 GAP catalysis, nuclear E3-ligase inhibition, ubiquitin-system control, and lysosomal cobalamin metabolism—are integrated and switched within one cell remains unresolved.
  • No unified model reconciling lysosomal GAP function with nuclear and metabolic roles
  • Upstream regulation determining which function dominates is unknown
  • Structural basis for context-dependent partner switching not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005634 nucleus 2 GO:0005764 lysosome 2
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-162582 Signal Transduction 2 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 2
Partners
HERC2NPRL3PDK1RAGARAGDRNF8RPTORUBE2M
Complex memberships
GATOR1

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 Arg-78 of NPRL2 functions as the catalytic arginine finger that executes GATOR1's GAP activity toward RagA, stimulating GTP hydrolysis. Substitution of Arg-78 renders mTORC1 signaling insensitive to amino acid starvation. This was established by site-directed mutagenesis, in vitro GTP hydrolysis assays, co-immunoprecipitation, and structural analysis. Site-directed mutagenesis, in vitro GTP hydrolysis assay, co-immunoprecipitation, structural analysis The Journal of biological chemistry High 30651352
2014 In Drosophila, Nprl2 and Nprl3 physically interact and co-localize to lysosomes and autolysosomes. Nprl2/3 inhibit TORC1 signaling in the female germline in response to amino acid starvation, and this inhibition is required to prevent apoptosis during nutrient scarcity. Nprl2/3 also work in concert with Tsc1/2 to fine-tune TORC1 activity. Co-immunoprecipitation, immunofluorescence localization, genetic loss-of-function, epistasis analysis with Tsc1/2 Cell death and differentiation High 24786828
2015 NPRL2 is required for mouse viability and fetal liver hematopoiesis. NPRL2 KO impairs lysosomal acidification and lysosomal gene expression, defective cobalamin-dependent methionine synthesis from homocysteine, and defective processing of the cobalamin-transport protein transcobalamin 2. These defects are rescued by cyanocobalamin supplementation, placing NPRL2 upstream of lysosomal-dependent cobalamin processing and methionine synthesis. Conditional knockout mouse model, metabolomics, cell fractionation, rescue experiments with cyanocobalamin Cell reports High 26166573
2008 NPRL2/TUSC4 forms a complex with PDK1 via its N-terminal 133 amino acid residues and suppresses Src-dependent tyrosine phosphorylation and activation of PDK1 in vitro and in cells. Deletion of the N-terminal domain abolishes this inhibitory effect, indicating complex formation is required for PDK1 inactivation. E. coli two-hybrid screening, co-immunoprecipitation, in vitro kinase assay, deletion mutagenesis, siRNA knockdown Cancer science Medium 18616680
2014 NPRL2/TUSC4 physically interacts with the E3 ubiquitin ligase HERC2, preventing BRCA1 degradation through the ubiquitination pathway. TUSC4 silencing enhances BRCA1 polyubiquitination and degradation, reducing homologous recombination repair efficiency. Co-immunoprecipitation, ubiquitination assay, gene expression profiling, HR repair assay Cancer research Medium 25480944
2015 NPRL2 interacts with Raptor in amino acid sufficiency to activate mTORC1, while it interacts with RagD (particularly RagA(GDP)/RagD(GTP) heterodimer) in amino acid scarcity to inhibit mTORC1. A reciprocal relationship exists between NPRL2 binding to Rag GTPases and Raptor, supporting a 'seesaw' model of mTORC1 regulation. Co-immunoprecipitation, dominant positive/negative Rag GTPase mutants, lysosomal localization by immunofluorescence, Drosophila genetic model Cellular signalling Medium 26582740
2017 Ectopic overexpression of NPRL2 in cells with active p53 induces NOX2-dependent reactive oxygen species production and DNA damage. Overexpressed NPRL2 accumulates in the nucleus together with apoptosis-inducing factor (AIF), triggering p53 phosphorylation, DNA damage response, and G1 arrest followed by apoptosis. In p53-negative cells, NPRL2 overexpression activates CHK1 or CHK2 and induces S or G2/M arrest. Overexpression, immunofluorescence, ROS assay, cell cycle analysis, co-localization with AIF Scientific reports Medium 29127423
2010 Yeast Npr2 (ortholog of human NPRL2) is a phosphorylation-dependent substrate of the SCF(Grr1) E3 ubiquitin ligase. Phosphorylation by casein kinases Yck1 and Yck2 destabilizes Npr2; it accumulates in grr1Δ mutants and is stabilized when the proteasome is inhibited. Npr2 is required for robust growth on ammonium or urea as nitrogen sources and for meiosis completion. Mass spectrometry interaction, genetic analysis of grr1Δ mutants, proteasome inhibition, overexpression lethality assay Eukaryotic cell Medium 20154027
2010 Restoration of NPRL2 in cisplatin-resistant NSCLC cells activates ATM kinase in response to cisplatin, promotes downstream γ-H2AX formation, increases CHK1 and CHK2 kinase activity, and elevates cell cycle checkpoint proteins CDC25A and CDC25C, leading to G2/M arrest and apoptosis. NPRL2 gene transfection/re-expression, Western blot for ATM/γ-H2AX/CHK1/CHK2/CDC25, flow cytometry for cell cycle, in vivo xenograft PloS one Medium 20700484
2022 Loss of NPRL2 in mouse excitatory glutamatergic neurons increases mTORC1-dependent signaling, reduces dendritic branching, and increases voltage-gated sodium channel expression (specifically Scn1A). Treatment with rapamycin prevents Scn1A upregulation, placing NPRL2-mTORC1 axis upstream of sodium channel regulation. Conditional neuronal knockout, electrophysiology (action potential recording), immunofluorescence, rapamycin rescue, primary neuron culture eNeuro Medium 35165201
2022 Neocortical loss of Nprl2 in mice increases mTORC1 signaling, causes spontaneous seizures, abnormal synaptic function (increased excitatory, decreased inhibitory currents), and elevates glycine levels. Glycine actions on NMDA receptors contribute to the electrophysiological and survival phenotypes, linking NPRL2 loss to altered amino acid/neurotransmitter metabolism. Conditional KO mouse, electrophysiology (EPSC/IPSC), proteomics, metabolomics, pharmacological NMDA receptor manipulation iScience Medium 35602938
2022 Conditional deletion of Nprl2 from mouse dorsal telencephalon (Emx1cre) causes spontaneous seizures and dysmorphic enlarged neuronal cells with increased mTORC1 signaling. Chronic rapamycin administration inhibits seizure occurrence and extends survival but does not rescue enlarged neuronal cells. Conditional knockout mouse model, EEG seizure recording, histology, rapamycin treatment Human molecular genetics Medium 34965576
2024 HSP70 mediates CHIP-induced polyubiquitination and proteasomal degradation of NPRL2. CHIP (the chaperone-associated E3 ubiquitin ligase) interacts with NPRL2 to promote its degradation; HSP70 overexpression enhances whereas HSP70 depletion inhibits amino acid-induced mTORC1 activation. HSP70 knockdown promotes basal autophagic flux and inhibits cell growth. Co-immunoprecipitation, ubiquitination assay, HSP70 overexpression/knockdown, mTORC1 activity assay, autophagy flux assay FASEB journal Medium 39495541
2021 NPRL2 interacts with UBE2M (a neddylation E2 enzyme), and this interaction increases NPRL2 protein stability by reducing its polyubiquitination and proteasomal degradation. NPRL2 cooperatively enhances UBE2M-mediated neddylation and facilitates degradation of substrates of Cullin-RING E3 ubiquitin ligases. Co-immunoprecipitation, immunofluorescence, ubiquitination assay, CCK-8, in vivo xenograft Experimental cell research Medium 33905671
2024 NPRL2 upregulates TRIM16 expression via inactivation of ERK1/2 signaling. TRIM16 in turn promotes ubiquitination-mediated degradation of Galectin-3 (Gal-3), reducing Gal-3 release from glioma cells. Secreted Gal-3 accelerates copper uptake and triggers cuproptosis in CD8+ T cells, so NPRL2 expression protects CD8+ T cells from cuproptosis in glioma. Co-immunoprecipitation, ubiquitination assay, flow cytometry for cuproptosis, Western blot for ERK signaling, clinical specimen correlation Cellular and molecular life sciences Medium 39367988
2025 Following radiation, NPRL2 translocates from the GATOR1 complex to the nucleus via AMPK-mediated phosphorylation of WDR24. In the nucleus, NPRL2 directly binds to the catalytic domains of E3 ubiquitin ligases HERC2 and RNF8, inactivating them and preventing degradation of DNA repair proteins, thereby promoting radioresistance. Nuclear fractionation, co-immunoprecipitation, AMPK inhibition, in vitro and in vivo radiosensitivity assays, domain binding assays Acta pharmaceutica Sinica. B Medium 41584340
2026 NPRL2 interacts with PRRSV Nsp1α via its C-terminal domain and mediates K63-linked ubiquitination of Nsp1α at lysine 150, targeting it for autophagic degradation. NPRL2 overexpression inhibits PRRSV replication; knockdown enhances viral propagation. Co-immunoprecipitation, ubiquitination assay (K63-linkage specific), autophagic flux assay (LC3-II), viral replication assay, domain mapping Veterinary research Medium 41742785
2004 NPRL2 protein contains a bipartite nuclear localization signal, a protein-binding domain, similarity to the MutS core domain, and a nitrogen permease regulator 2 domain. The yeast ortholog NPR2 shares 32-36% identity. Re-expression of NPRL2 suppresses tumor growth in SCID mice and inhibits tumor cell growth in vitro. Sequence analysis, tet-controlled transgene expression, SCID mouse tumor suppression assay Cancer research Low 15374952

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy. Annals of neurology 180 26505888
2004 Functional characterization of the candidate tumor suppressor gene NPRL2/G21 located in 3p21.3C. Cancer research 62 15374952
2006 The 3p21.3 tumor suppressor NPRL2 plays an important role in cisplatin-induced resistance in human non-small-cell lung cancer cells. Cancer research 60 17018626
2019 Arg-78 of Nprl2 catalyzes GATOR1-stimulated GTP hydrolysis by the Rag GTPases. The Journal of biological chemistry 55 30651352
2014 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. Cell death and differentiation 45 24786828
2010 Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer. BMC cancer 44 20193080
2018 NPRL2 enhances autophagy and the resistance to Everolimus in castration-resistant prostate cancer. The Prostate 42 30178500
2015 Regulation of Hematopoiesis and Methionine Homeostasis by mTORC1 Inhibitor NPRL2. Cell reports 40 26166573
2010 NPRL2 sensitizes human non-small cell lung cancer (NSCLC) cells to cisplatin treatment by regulating key components in the DNA repair pathway. PloS one 33 20700484
2014 TUSC4 functions as a tumor suppressor by regulating BRCA1 stability. Cancer research 28 25480944
2008 TUSC4/NPRL2, a novel PDK1-interacting protein, inhibits PDK1 tyrosine phosphorylation and its downstream signaling. Cancer science 27 18616680
2008 [Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer]. Molekuliarnaia biologiia 25 19140316
2010 Npr2, yeast homolog of the human tumor suppressor NPRL2, is a target of Grr1 required for adaptation to growth on diverse nitrogen sources. Eukaryotic cell 21 20154027
2022 Dorsal telencephalon-specific Nprl2- and Nprl3-knockout mice: novel mouse models for GATORopathy. Human molecular genetics 20 34965576
2020 NPRL2 promotes docetaxel chemoresistance in castration resistant prostate cancer cells by regulating autophagy through the mTOR pathway. Experimental cell research 20 32234375
2017 Tumor suppressor NPRL2 induces ROS production and DNA damage response. Scientific reports 19 29127423
2021 FOXO1 inhibits prostate cancer cell proliferation via suppressing E2F1 activated NPRL2 expression. Cell biology international 15 34459063
2015 Functional mechanism of the enhancement of 5-fluorouracil sensitivity by TUSC4 in colon cancer cells. Oncology letters 15 26788191
2014 Decreased expression of NPRL2 in renal cancer cells is associated with unfavourable pathological, proliferation and apoptotic features. Pathology oncology research : POR 14 24789683
2019 The TORC1 inhibitor Nprl2 protects age-related digestive function in Drosophila. Aging 12 31712450
2014 Relationship between tumor and peripheral blood NPRL2 mRNA levels in patients with colorectal adenoma and colorectal cancer. Cancer biology & therapy 11 24521741
2018 Targeting NPRL2 to enhance the efficacy of Olaparib in castration-resistant prostate cancer. Biochemical and biophysical research communications 10 30522863
2022 NPRL2 Inhibition of mTORC1 Controls Sodium Channel Expression and Brain Amino Acid Homeostasis. eNeuro 9 35165201
2021 A splicing variation in NPRL2 causing familial focal epilepsy with variable foci: additional cases and literature review. Journal of human genetics 9 34376795
2015 Amino acid-dependent NPRL2 interaction with Raptor determines mTOR Complex 1 activation. Cellular signalling 9 26582740
2022 NPRL2 down-regulation facilitates the growth of hepatocellular carcinoma via the mTOR pathway and autophagy suppression. Hepatology communications 8 36321403
2021 Phenotypic and Genotypic Characterization of NPRL2-Related Epilepsy: Two Case Reports and Literature Review. Frontiers in neurology 8 34912289
2018 Overexpression of Nitrogen Permease Regulator Like-2 (NPRL2) Enhances Sensitivity to Irinotecan (CPT-11) in Colon Cancer Cells by Activating the DNA Damage Checkpoint Pathway. Medical science monitor : international medical journal of experimental and clinical research 8 29519997
2025 NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic non-small cell lung cancer (NSCLC) in a humanized mouse model. eLife 6 39932765
2024 NPRL2 promotes TRIM16-mediated ubiquitination degradation of Galectin-3 to prevent CD8+T lymphocyte cuproptosis in glioma. Cellular and molecular life sciences : CMLS 6 39367988
2022 Increased glycine contributes to synaptic dysfunction and early mortality in Nprl2 seizure model. iScience 6 35602938
2021 NPRL2 reduces the niraparib sensitivity of castration-resistant prostate cancer via interacting with UBE2M and enhancing neddylation. Experimental cell research 6 33905671
2023 Clinical phenotype and genotype of NPRL2-related epilepsy: Four cases reports and literature review. Seizure 3 37741786
2016 Biological characteristics of renal cancer cells after CTP-mediated cancer suppressor gene NPRL2 protein treatment. Biological chemistry 3 27186678
2025 Explosive onset focal epilepsies without cortical malformation: A review of a pediatric cohort with pathogenic variations in the GATOR1 complex (DEPDC5, NPRL3 and NPRL2). Seizure 1 40188669
2025 Everolimus precision therapy in NPRL2- and NPRL3-related epilepsy. Epilepsia 1 40956028
2025 Genotypic and phenotypic analysis of epilepsy associated with NPRL2/NPRL3 genes. Seizure 1 41197257
2024 HSP70 promotes amino acid-dependent mTORC1 signaling by mediating CHIP-induced NPRL2 ubiquitination and degradation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 39495541
2023 [The regulatory relationship between RagA and Nprl2 in Drosophila gut development]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 1 37154336
2026 NPRL2 restricts porcine reproductive and respiratory syndrome virus replication by targeting viral Nsp1α for autophagic degradation. Veterinary research 0 41742285
2026 Citrus aurantium honey-mediated gut homeostasis and anti-inflammation via Thorl/Nprl2-TORC1 signaling: Network pharmacology and Drosophila validation. Animal models and experimental medicine 0 42226584
2025 Neuronal cell type specific roles for Nprl2 in neurodevelopmental disorder-relevant behaviors. Neurobiology of disease 0 39765274
2025 Incomplete penetrance and variable phenotypes of a novel NPRL2 frameshift variant: from familial focal epilepsy with variable foci 2 to neurodevelopmental disorders. BMC neurology 0 40804712
2025 Intrinsic NPRL2 and NPRL3 regulate the sensitivity of B-cell malignancies to CAR-T cell therapy. Journal of genetics and genomics = Yi chuan xue bao 0 41260247
2025 Radiation-induced nuclear translocation of NPRL2 hijacks E3 ubiquitin ligases to enhance DNA repair via the AMPK/WDR24 axis, contributing to CRC radioresistance. Acta pharmaceutica Sinica. B 0 41584340
2024 Establishment of a transgene-free iPS cell line (SDCHi003-A) from a young patient bearing a NPRL2 mutation and suffering from Epilepsy. Stem cell research 0 38430737
2024 NPRL2 is required for proliferation of oncogenic Ras-transformed bronchial epithelial cells. Cell division 0 38915098
2023 Risk signature identification and NPRL2 affects sunitinib sensitivity in clear cell renal cell carcinoma. Biochemical and biophysical research communications 0 37121122
2012 [Effect of recombinant plasmid pEGFP-N1-NPRL2 on the biological characteristics of human gastric cancer cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 23046930

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