{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:24:39Z","timestamp":1790634279365,"version":"4.1.0"},"reference-count":146,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Myo-inositol belongs to one of the sugar alcohol groups known as cyclitols. Phosphatidylinositols are one of the derivatives of Myo-inositol, and constitute important mediators in many intracellular processes such as cell growth, cell differentiation, receptor recycling, cytoskeletal organization, and membrane fusion. They also have even more functions that are essential for cell survival. Mutations in genes encoding phosphatidylinositols and their derivatives can lead to many disorders. This review aims to perform an in-depth analysis of these connections. Many authors emphasize the significant influence of phosphatidylinositols and phosphatidylinositols\u2019 phosphates in the pathogenesis of myotubular myopathies, neurodegenerative disorders, carcinogenesis, and other less frequently observed diseases. In our review, we have focused on three of the most often mentioned groups of disorders. Inositols are the topic of many studies, and yet, there are no clear results of successful clinical trials. Analysis of the available literature gives promising results and shows that further research is still needed.<\/jats:p>","DOI":"10.3390\/biom13101550","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T07:15:36Z","timestamp":1697699736000},"page":"1550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Genetic Background of Abnormalities in Metabolic Pathways of Phosphoinositides and Their Linkage with the Myotubular Myopathies, Neurodegenerative Disorders, and Carcinogenesis"],"prefix":"10.3390","volume":"13","author":[{"given":"Maria","family":"Derkaczew","sequence":"first","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"},{"name":"Students\u2019 Scientific Club of Pathophysiologists, Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Martyniuk","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"},{"name":"Students\u2019 Scientific Club of Pathophysiologists, Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hofman","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"},{"name":"Students\u2019 Scientific Club of Pathophysiologists, Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4417-7318","authenticated-orcid":false,"given":"Krzysztof","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Club of Pathophysiologists, Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury, 10-082 Olsztyn, Poland"},{"name":"The Nicolaus Copernicus Municipal Polyclinical Hospital in Olsztyn, 10-045 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0544-5653","authenticated-orcid":false,"given":"Adam","family":"Osowski","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0856-3644","authenticated-orcid":false,"given":"Joanna","family":"Wojtkiewicz","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1432-1033.1990.tb19297.x","article-title":"myo-Inositol Metabolites as Cellular Signals","volume":"193","author":"Downes","year":"1990","journal-title":"Eur. J. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Derkaczew, M., Martyniuk, P., Osowski, A., and Wojtkiewicz, J. (2023). Cyclitols: From Basic Understanding to Their Association with Neurodegeneration. Nutrients, 15.","DOI":"10.3390\/nu15092029"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1042\/BST0371139","article-title":"Investigation of the H+\u2013 Myo -Inositol Transporter (HMIT) as a Neuronal Regulator of Phosphoinositide Signalling","volume":"37","author":"Daniel","year":"2009","journal-title":"Biochem. Soc. Trans."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/j.biochi.2013.05.011","article-title":"Potential Role and Therapeutic Interests of Myo-Inositol in Metabolic Diseases","volume":"95","author":"Croze","year":"2013","journal-title":"Biochimie"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.febslet.2015.03.012","article-title":"Inositol Transport Proteins","volume":"589","author":"Schneider","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1080\/17425255.2016.1206887","article-title":"Pharmacodynamics and Pharmacokinetics of Inositol(s) in Health and Disease","volume":"12","author":"Bizzarri","year":"2016","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s11154-016-9370-3","article-title":"Inositol(s) in Thyroid Function, Growth and Autoimmunity","volume":"17","author":"Benvenga","year":"2016","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"De Craene, J.-O., Bertazzi, D., B\u00e4r, S., and Friant, S. (2017). Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030634"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0166-6851(94)90054-X","article-title":"Characterization of Phosphatidylinositol Synthase and Evidence of a Polyphosphoinositide Cycle in Plasmodium-Infected Erythrocytes","volume":"63","author":"Elabbadi","year":"1994","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1006\/scdb.2000.0235","article-title":"Phosphatidylinositol Transfer Proteins Couple Lipid Transport to Phosphoinositide Synthesis","volume":"12","author":"Cockcroft","year":"2001","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Devereaux, K., Dall\u2019Armi, C., Alcazar-Roman, A., Ogasawara, Y., Zhou, X., Wang, F., Yamamoto, A., De Camilli, P., and Di Paolo, G. (2013). Regulation of Mammalian Autophagy by Class II and III PI 3-Kinases through PI3P Synthesis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076405"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33076","DOI":"10.1074\/jbc.M507201200","article-title":"HVps34 Is a Nutrient-Regulated Lipid Kinase Required for Activation of P70 S6 Kinase","volume":"280","author":"Byfield","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.bbalip.2007.01.015","article-title":"Synthesis and Function of Membrane Phosphoinositides in Budding Yeast, Saccharomyces Cerevisiae","volume":"1771","author":"Strahl","year":"2007","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BCJ20180022","article-title":"Understanding Phosphoinositides: Rare, Dynamic, and Essential Membrane Phospholipids","volume":"476","author":"Dickson","year":"2019","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1104\/pp.109.146159","article-title":"Arabidopsis FAB1\/PIKfyve Proteins Are Essential for Development of Viable Pollen","volume":"151","author":"Whitley","year":"2009","journal-title":"Plant Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Buckley, C.M., Heath, V.L., Gu\u00e9ho, A., Bosmani, C., Knobloch, P., Sikakana, P., Personnic, N., Dove, S.K., Michell, R.H., and Meier, R. (2019). PIKfyve\/Fab1 Is Required for Efficient V-ATPase and Hydrolase Delivery to Phagosomes, Phagosomal Killing, and Restriction of Legionella Infection. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007551"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21589","DOI":"10.1074\/jbc.274.31.21589","article-title":"PIKfyve, a Mammalian Ortholog of Yeast Fab1p Lipid Kinase, Synthesizes 5-Phosphoinositides","volume":"274","author":"Sbrissa","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rajala, A., Rajala, R., Teel, K., and Rajala, R.V.S. (2022). Ribosomal Targeting Strategy and Nuclear Labeling to Analyze Photoreceptor Phosphoinositide Signatures. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1867.","DOI":"10.1016\/j.bbalip.2022.159161"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lu, N., Shen, Q., Mahoney, T.R., Neukomm, L.J., Wang, Y., and Zhou, Z. (2012). Two PI 3-Kinases and One PI 3-Phosphatase Together Establish the Cyclic Waves of Phagosomal PtdIns(3)P Critical for the Degradation of Apoptotic Cells. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001245"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4652","DOI":"10.1038\/s41467-023-40428-1","article-title":"Deterministic Early Endosomal Maturations Emerge from a Stochastic Trigger-and-Convert Mechanism","volume":"14","author":"York","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_21","unstructured":"Godi, A. (2002). Regulation and Molecular Composition of the Golgi-Associated Spectrin Skeleton. [Ph.D. Thesis, Open University (United Kingdom)]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1091\/mbc.12.8.2396","article-title":"Sac1 Lipid Phosphatase and Stt4 Phosphatidylinositol 4-Kinase Regulate a Pool of Phosphatidylinositol 4-Phosphate That Functions in the Control of the Actin Cytoskeleton and Vacuole Morphology","volume":"12","author":"Foti","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_23","unstructured":"B\u00f6ttcher-Sehlmeyer, C. (2006). Subcellular Localization and Molecular Interactions of Phosphoinositide 5\u2032-Phosphatases of the Yeast Synaptojanin-like Protein Family. [Ph.D. Thesis, University of Stuttgart]."},{"key":"ref_24","unstructured":"Ebrahimzadeh, Z. (2019). Exploring the Roles of Phosphoinositides in the Biology of the Malaria Parasite Plasmodium Falciparum. [Ph.D. Thesis, Universit\u00e9 Laval]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1111\/j.1600-0854.2005.00311.x","article-title":"Structure and Function of the Lowe Syndrome Protein OCRL1: Structure and Function of OCRL1","volume":"6","author":"Lowe","year":"2005","journal-title":"Traffic"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/tra.12160","article-title":"The Cellular and Physiological Functions of the Lowe Syndrome Protein OCRL1","volume":"15","author":"Mehta","year":"2014","journal-title":"Traffic"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.37349\/ent.2021.00008","article-title":"Striking a Balance: PIP2 and PIP3 Signaling in Neuronal Health and Disease","volume":"1","author":"Tariq","year":"2021","journal-title":"Explor. Neuroprot. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bbamcr.2005.04.013","article-title":"The Role of the Phosphoinositides at the Golgi Complex","volume":"1744","author":"Godi","year":"2005","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/nature09023","article-title":"The PtdIns(3,4)P2 Phosphatase INPP4A Is a Suppressor of Excitotoxic Neuronal Death","volume":"465","author":"Sasaki","year":"2010","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1091\/mbc.e04-09-0799","article-title":"The Type I\u03b1 Inositol Polyphosphate 4-Phosphatase Generates and Terminates Phosphoinositide 3-Kinase Signals on Endosomes and the Plasma Membrane","volume":"16","author":"Ivetac","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/j.bbamcr.2018.07.013","article-title":"Novel Nuclear Translocation of Inositol Polyphosphate 4-Phosphatase Is Associated with Cell Cycle, Proliferation and Survival","volume":"1865","author":"Chaudhuri","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_32","first-page":"1999","article-title":"Inositol Phosphatase INPP4A Inhibits the Apoptosis of in Vitro Neurons with Characteristic of Intractable Epilepsy by Reducing Intracellular Ca2+ Concentration","volume":"11","author":"Wang","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.bbrc.2013.09.077","article-title":"Determinants of the Tumor Suppressor INPP4B Protein and Lipid Phosphatase Activities","volume":"440","author":"Lopez","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E978","DOI":"10.1073\/pnas.1311029111","article-title":"Sequential Breakdown of 3-Phosphorylated Phosphoinositides Is Essential for the Completion of Macropinocytosis","volume":"111","author":"Maekawa","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ccr.2009.06.006","article-title":"Evidence That Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor That Inhibits PI3K Signaling","volume":"16","author":"Gewinner","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.2147\/IJN.S112030","article-title":"Amorphous Silica Nanoparticles Trigger Vascular Endothelial Cell Injury through Apoptosis and Autophagy via Reactive Oxygen Species-Mediated MAPK\/Bcl-2 and PI3K\/Akt\/MTOR Signaling","volume":"11","author":"Guo","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8287","DOI":"10.2147\/OTT.S223221","article-title":"INPP4B As A Prognostic and Diagnostic Marker Regulates Cell Growth of Pancreatic Cancer Via Activating AKT","volume":"12","author":"Zhai","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9370","DOI":"10.1074\/jbc.270.16.9370","article-title":"Properties of Type II Inositol Polyphosphate 5-Phosphatase","volume":"270","author":"Jefferson","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/s00335-010-9281-7","article-title":"Species-Specific Difference in Expression and Splice-Site Choice in Inpp5b, an Inositol Polyphosphate 5-Phosphatase Paralogous to the Enzyme Deficient in Lowe Syndrome","volume":"21","author":"Bothwell","year":"2010","journal-title":"Mamm. Genome"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1093\/oxfordjournals.hmg.a018913","article-title":"Myotubularin, a Phosphatase Deficient in Myotubular Myopathy, Acts on Phosphatidylinositol 3-Kinase and Phosphatidylinositol 3-Phosphate Pathway","volume":"9","author":"Blondeau","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8910","DOI":"10.1073\/pnas.160255697","article-title":"Myotubularin, a Protein Tyrosine Phosphatase Mutated in Myotubular Myopathy, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3-Phosphate","volume":"97","author":"Taylor","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0960-9822(03)00132-5","article-title":"Phosphatidylinositol-5-Phosphate Activation and Conserved Substrate Specificity of the Myotubularin Phosphatidylinositol 3-Phosphatases","volume":"13","author":"Schaletzky","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13817","DOI":"10.1074\/jbc.M312294200","article-title":"Myotubularin Regulates the Function of the Late Endosome through the GRAM Domain-Phosphatidylinositol 3,5-Bisphosphate Interaction","volume":"279","author":"Tsujita","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Gupta, V.A., Hnia, K., Smith, L.L., Gundry, S.R., McIntire, J.E., Shimazu, J., Bass, J.R., Talbot, E.A., Amoasii, L., and Goldman, N.E. (2013). Loss of Catalytically Inactive Lipid Phosphatase Myotubularin-Related Protein 12 Impairs Myotubularin Stability and Promotes Centronuclear Myopathy in Zebrafish. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003583"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.nmd.2021.08.003","article-title":"X-Linked Myotubular Myopathy","volume":"31","author":"Lawlor","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.1074\/jbc.M111087200","article-title":"Myotubularin and MTMR2, Phosphatidylinositol 3-Phosphatases Mutated in Myotubular Myopathy and Type 4B Charcot-Marie-Tooth Disease","volume":"277","author":"Kim","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bong, S.M., Son, K., Yang, S.-W., Park, J.-W., Cho, J.-W., Kim, K.-T., Kim, H., Kim, S.J., Kim, Y.J., and Lee, B.I. (2016). Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152611"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/S0960-9822(01)00501-2","article-title":"Characterization of MTMR3: An Inositol Lipid 3-Phosphatase with Novel Substrate Specificity","volume":"11","author":"Walker","year":"2001","journal-title":"Curr. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1006\/excr.2001.5185","article-title":"FYVE-DSP2, a FYVE Domain-Containing Dual Specificity Protein Phosphatase That Dephosphorylates Phosphotidylinositol 3-Phosphate","volume":"265","author":"Zhao","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10461","DOI":"10.1073\/pnas.1501752112","article-title":"MTMR3 Risk Allele Enhances Innate Receptor-Induced Signaling and Cytokines by Decreasing Autophagy and Increasing Caspase-1 Activation","volume":"112","author":"Lahiri","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8412","DOI":"10.1074\/jbc.RA118.005731","article-title":"PtdIns3P Phosphatases MTMR3 and MTMR4 Negatively Regulate Innate Immune Responses to DNA through Modulating STING Trafficking","volume":"294","author":"Kawasaki","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1042\/BJ20081866","article-title":"The Inositol Phosphatase MTMR4 Is a Novel Target of the Ubiquitin Ligase Nedd4","volume":"419","author":"Plant","year":"2009","journal-title":"Biochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1021\/acs.jproteome.7b00065","article-title":"A Human Tyrosine Phosphatase Interactome Mapped by Proteomic Profiling","volume":"16","author":"Kumar","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1242\/jcs.060103","article-title":"The Myotubularin Phosphatase MTMR4 Regulates Sorting from Early Endosomes","volume":"123","author":"Naughtin","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1074\/jbc.M804292200","article-title":"MTMR9 Increases MTMR6 Enzyme Activity, Stability, and Role in Apoptosis","volume":"284","author":"Zou","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9539","DOI":"10.1073\/pnas.1207021109","article-title":"Myotubularin-Related Protein (MTMR) 9 Determines the Enzymatic Activity, Substrate Specificity, and Role in Autophagy of MTMR8","volume":"109","author":"Zou","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1128\/MCB.25.9.3630-3638.2005","article-title":"The Phosphatidylinositol 3-Phosphate Phosphatase Myotubularin- Related Protein 6 (MTMR6) Is a Negative Regulator of the Ca2+-Activated K+ Channel KCa3","volume":"25","author":"Srivastava","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1074\/jbc.M112.395087","article-title":"Phosphatidylinositol 3-Phosphatase Myotubularin-Related Protein 6 (MTMR6) Is Regulated by Small GTPase Rab1B in the Early Secretory and Autophagic Pathways","volume":"288","author":"Mochizuki","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"50490","DOI":"10.18632\/oncotarget.10466","article-title":"Myotubularin-Related Protein 7 Inhibits Insulin Signaling in Colorectal Cancer","volume":"7","author":"Weidner","year":"2016","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1080\/15384101.2019.1661174","article-title":"Myotubularin Related Protein 7 Is Essential for the Spermatogonial Stem Cell Homeostasis via PI3K\/AKT Signaling","volume":"18","author":"Zhao","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1487.e21","DOI":"10.1016\/j.neurobiolaging.2011.10.011","article-title":"Genome-Wide Study Links MTMR7 Gene to Variant Creutzfeldt-Jakob Risk","volume":"33","author":"Bishop","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41389-020-0238-8","article-title":"Myotubularin-Related Protein 7 Activates Peroxisome Proliferator-Activated Receptor-Gamma","volume":"9","author":"Weidner","year":"2020","journal-title":"Oncogenesis"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1107\/S139900471500927X","article-title":"Structure of the Catalytic Phosphatase Domain of MTMR8: Implications for Dimerization, Membrane Association and Reversible Oxidation","volume":"71","author":"Yoo","year":"2015","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/bib\/bbr042","article-title":"Phylogenetic-Based Propagation of Functional Annotations within the Gene Ontology Consortium","volume":"12","author":"Gaudet","year":"2011","journal-title":"Brief. Bioinform."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrneph.2017.83","article-title":"The 5-Phosphatase OCRL in Lowe Syndrome and Dent Disease 2","volume":"13","author":"Staiano","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/s41590-020-0730-5","article-title":"STEEP Mediates STING ER Exit and Activation of Signaling","volume":"21","author":"Zhang","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1016\/j.yexcr.2010.07.008","article-title":"A Phosphatidylinositol 3-Kinase Class III Sub-Complex Containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 Regulates Cytokinesis and Degradative Endocytic Traffic","volume":"316","author":"Thoresen","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1128\/JVI.01392-15","article-title":"Genome-Wide Mapping of the Binding Sites and Structural Analysis of Kaposi\u2019s Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 2 Reveal That It Is a DNA-Binding Transcription Factor","volume":"90","author":"Hu","year":"2016","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K Pathway in Human Disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1056\/NEJMe1400055","article-title":"Idelalisib\u2014A PI3K\u03b4 Inhibitor for B-Cell Cancers","volume":"370","author":"Fruman","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2174\/138920207782446160","article-title":"The Phosphoinositide 3-Kinase Pathway in Human Cancer: Genetic Alterations and Therapeutic Implications","volume":"8","author":"Arcaro","year":"2007","journal-title":"Curr. Genom."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s12035-012-8358-6","article-title":"Phosphatidylinositol 4-Kinases and PI4P Metabolism in the Nervous System: Roles in Psychiatric and Neurological Diseases","volume":"47","author":"Clayton","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1038\/ncomms4552","article-title":"Molecular Insights into the Membrane-Associated Phosphatidylinositol 4-Kinase II\u03b1","volume":"5","author":"Zhou","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/s41388-019-1010-4","article-title":"Therapeutic Targeting of the PI4K2A\/PKR Lysosome Network Is Critical for Misfolded Protein Clearance and Survival in Cancer Cells","volume":"39","author":"Pataer","year":"2020","journal-title":"Oncogene"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S1388-1981(99)00029-3","article-title":"Functional Expression and Characterisation of a New Human Phosphatidylinositol 4-Kinase PI4K230","volume":"1437","author":"Gehrmann","year":"1999","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1083\/jcb.201206095","article-title":"PtdIns4P Synthesis by PI4KIII\u03b1 at the Plasma Membrane and Its Impact on Plasma Membrane Identity","volume":"199","author":"Nakatsu","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3732","DOI":"10.1093\/hmg\/ddv117","article-title":"Germline Recessive Mutations in PI4KA Are Associated with Perisylvian Polymicrogyria, Cerebellar Hypoplasia and Arthrogryposis","volume":"24","author":"Pagnamenta","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/978-94-007-5025-8_7","article-title":"PIKfyve and Its Lipid Products in Health and in Sickness","volume":"Volume 362","author":"Falasca","year":"2012","journal-title":"Phosphoinositides and Disease"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9229","DOI":"10.1158\/0008-5472.CAN-07-1333","article-title":"The Phosphoinositide Kinase PIKfyve Mediates Epidermal Growth Factor Receptor Trafficking to the Nucleus","volume":"67","author":"Kim","year":"2007","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"23878","DOI":"10.1074\/jbc.M611678200","article-title":"Core Protein Machinery for Mammalian Phosphatidylinositol 3,5-Bisphosphate Synthesis and Turnover That Regulates the Progression of Endosomal Transport","volume":"282","author":"Sbrissa","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"C436","DOI":"10.1152\/ajpcell.00105.2012","article-title":"Functional Dissociation between PIKfyve-Synthesized PtdIns5P and PtdIns(3,5)P2 by Means of the PIKfyve Inhibitor YM201636","volume":"303","author":"Sbrissa","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.devcel.2016.08.001","article-title":"PIKfyve Regulates Vacuole Maturation and Nutrient Recovery Following Engulfment","volume":"38","author":"Krishna","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.4049\/jimmunol.1601466","article-title":"The Lipid Kinase PIKfyve Coordinates the Neutrophil Immune Response through the Activation of the Rac GTPase","volume":"199","author":"Dayam","year":"2017","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Liggins, M.C., Flesher, J.L., Jahid, S., Vasudeva, P., Eby, V., Takasuga, S., Sasaki, J., Sasaki, T., Boissy, R.E., and Ganesan, A.K. (2018). PIKfyve Regulates Melanosome Biogenesis. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007290"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.isci.2018.12.015","article-title":"The Phosphoinositide Kinase PIKfyve Promotes Cathepsin-S-Mediated Major Histocompatibility Complex Class II Antigen Presentation","volume":"11","author":"Baranov","year":"2019","journal-title":"iScience"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.3324\/haematol.2019.222729","article-title":"Identification of PIKfyve Kinase as a Target in Multiple Myeloma","volume":"105","author":"Zhu","year":"2020","journal-title":"Haematologica"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0092-8674(02)00745-6","article-title":"Tumor Suppressor PTEN Mediates Sensing of Chemoattractant Gradients","volume":"109","author":"Iijima","year":"2002","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0092-8674(02)00755-9","article-title":"Spatial and Temporal Regulation of 3-Phosphoinositides by PI 3-Kinase and PTEN Mediates Chemotaxis","volume":"109","author":"Funamoto","year":"2002","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1242\/jcs.010876","article-title":"PTEN Plays a Role in the Suppression of Lateral Pseudopod Formation during Dictyostelium Motility and Chemotaxis","volume":"120","author":"Wessels","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.arr.2008.04.003","article-title":"Oscillatory Signaling and Network Responses during the Development of Dictyostelium Discoideum","volume":"7","author":"McMains","year":"2008","journal-title":"Ageing Res. Rev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1529\/biophysj.108.130179","article-title":"3\u2032-Phosphoinositides Regulate the Coordination of Speed and Accuracy during Chemotaxis","volume":"95","author":"Gruver","year":"2008","journal-title":"Biophys. J."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Maeda, Y.T., Inose, J., Matsuo, M.Y., Iwaya, S., and Sano, M. (2008). Ordered Patterns of Cell Shape and Orientational Correlation during Spontaneous Cell Migration. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003734"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1097\/GIM.0b013e3181ac9aea","article-title":"PTEN Hamartoma Tumor Syndrome","volume":"11","author":"Yehia","year":"2009","journal-title":"Genet. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1105\/tpc.105.031377","article-title":"Mutation of SAC1, an Arabidopsis SAC Domain Phosphoinositide Phosphatase, Causes Alterations in Cell Morphogenesis, Cell Wall Synthesis, and Actin Organization","volume":"17","author":"Zhong","year":"2005","journal-title":"Plant Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/tra.12554","article-title":"Sac1, a Lipid Phosphatase at the Interface of Vesicular and Nonvesicular Transport","volume":"19","author":"Brill","year":"2018","journal-title":"Traffic"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nature02046","article-title":"Global Analysis of Protein Expression in Yeast","volume":"425","author":"Ghaemmaghami","year":"2003","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1093\/brain\/aww180","article-title":"Loss of SYNJ1 Dual Phosphatase Activity Leads to Early Onset Refractory Seizures and Progressive Neurological Decline","volume":"139","author":"Hardies","year":"2016","journal-title":"Brain"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1002\/humu.22373","article-title":"Mutation in the SYNJ1 Gene Associated with Autosomal Recessive, Early-Onset Parkinsonism","volume":"34","author":"Quadri","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1042\/bj3600277","article-title":"TPIP: A Novel Phosphoinositide 3-Phosphatase","volume":"360","author":"Walker","year":"2001","journal-title":"Biochem. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1750-1172-3-26","article-title":"Centronuclear (Myotubular) Myopathy","volume":"3","author":"Jungbluth","year":"2008","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s40478-020-01048-8","article-title":"RAAV-Related Therapy Fully Rescues Myonuclear and Myofilament Function in X-Linked Myotubular Myopathy","volume":"8","author":"Ross","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"220ra10","DOI":"10.1126\/scitranslmed.3007523","article-title":"Gene Therapy Prolongs Survival and Restores Function in Murine and Canine Models of Myotubular Myopathy","volume":"6","author":"Childers","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1093\/hmg\/ddt003","article-title":"Enzyme Replacement Therapy Rescues Weakness and Improves Muscle Pathology in Mice with X-Linked Myotubular Myopathy","volume":"22","author":"Lawlor","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e151933","DOI":"10.1172\/jci.insight.151933","article-title":"Inactivating the Lipid Kinase Activity of PI3KC2\u03b2 Is Sufficient to Rescue Myotubular Myopathy in Mice","volume":"8","author":"Goret","year":"2023","journal-title":"JCI Insight"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1172\/JCI71206","article-title":"Reducing Dynamin 2 Expression Rescues X-Linked Centronuclear Myopathy","volume":"124","author":"Cowling","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"eaav1866","DOI":"10.1126\/scitranslmed.aav1866","article-title":"Amphiphysin 2 Modulation Rescues Myotubular Myopathy and Prevents Focal Adhesion Defects in Mice","volume":"11","author":"Lionello","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399407000439","article-title":"Charcot\u2013Marie\u2013Tooth Type 4B Demyelinating Neuropathy: Deciphering the Role of MTMR Phosphatases","volume":"9","author":"Previtali","year":"2007","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1212\/NXG.0000000000000061","article-title":"\u201cFork and Bracket\u201d Syndrome Expands the Spectrum of SBF1 -Related Sensory Motor Polyneuropathies","volume":"2","author":"Romani","year":"2016","journal-title":"Neurol. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1469-1809.2007.00412.x","article-title":"Charcot-Marie-Tooth Disease: A Clinico-Genetic Confrontation: Charcot-Marie-Tooth Disease","volume":"72","author":"Barisic","year":"2008","journal-title":"Ann. Hum. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Dugger, B.N., and Dickson, D.W. (2017). Pathology of Neurodegenerative Diseases. Cold Spring Harb. Perspect. Biol., 9.","DOI":"10.1101\/cshperspect.a028035"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e10248","DOI":"10.15252\/emmm.201810248","article-title":"Inflammasomes in Neuroinflammatory and Neurodegenerative Diseases","volume":"11","author":"Voet","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"375","DOI":"10.2217\/14622416.7.3.375","article-title":"Gene Expression Profile of Empirically Delineated Classes of Unexplained Chronic Fatigue","volume":"7","author":"Carmel","year":"2006","journal-title":"Pharmacogenomics"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1089\/adt.2017.790","article-title":"Development of Three Orthogonal Assays Suitable for the Identification and Qualification of PIKfyve Inhibitors","volume":"15","author":"Fogarty","year":"2017","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"17518","DOI":"10.1073\/pnas.0702275104","article-title":"Loss of Vac14, a Regulator of the Signaling Lipid Phosphatidylinositol 3,5-Bisphosphate, Results in Neurodegeneration in Mice","volume":"104","author":"Zhang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/bies.201300012","article-title":"Phosphatidylinositol 3,5-Bisphosphate: Low Abundance, High Significance: Prospects & Overviews","volume":"36","author":"McCartney","year":"2014","journal-title":"BioEssays"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/S0002-9440(10)61197-2","article-title":"Deregulation of the Phosphatidylinositol-3 Kinase Signaling Cascade Is Associated with Neurodegeneration in Npc1\u2212\/\u2212 Mouse Brain","volume":"167","author":"Bi","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"222","DOI":"10.4161\/auto.3822","article-title":"Altered Regulation of Phosphatidylinositol 3-Kinase Signaling in Cathepsin D-Deficient Brain","volume":"3","author":"Walls","year":"2007","journal-title":"Autophagy"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1021\/acs.jmedchem.1c01819","article-title":"Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase \u03b3 Inhibitors with a Non-ATP-Competitive, Allosteric Binding Mode","volume":"65","author":"Boffey","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"115027","DOI":"10.1016\/j.ejmech.2022.115027","article-title":"Development of Potent and Selective Degraders of PI5P4K\u03b3","volume":"247","author":"Ji","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/nan.12056","article-title":"Phosphatidylinositol-4,5-bisphosphate Is Enriched in Granulovacuolar Degeneration Bodies and Neurofibrillary Tangles","volume":"40","author":"Nishikawa","year":"2014","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"19524","DOI":"10.1073\/pnas.0604954103","article-title":"Presenilin Mutations Linked to Familial Alzheimer\u2019s Disease Cause an Imbalance in Phosphatidylinositol 4,5-Bisphosphate Metabolism","volume":"103","author":"Landman","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12964-021-00715-0","article-title":"Phosphoinositides Signaling Modulates Microglial Actin Remodeling and Phagocytosis in Alzheimer\u2019s Disease","volume":"19","author":"Desale","year":"2021","journal-title":"Cell Commun. Signal"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1093\/toxsci\/kfy184","article-title":"The Evolution of Carcinogenesis","volume":"165","author":"Peters","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0098-2997(00)00007-8","article-title":"The Molecular Biology of Cancer","volume":"21","author":"Bertram","year":"2001","journal-title":"Mol. Asp. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"118513","DOI":"10.1016\/j.lfs.2020.118513","article-title":"PI3K\/AKT\/MTOR Signaling in Gastric Cancer: Epigenetics and Beyond","volume":"262","author":"Fattahi","year":"2020","journal-title":"Life Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.semcancer.2019.05.012","article-title":"Role of the PI3K\/AKT\/MTOR Signaling Pathway in Ovarian Cancer: Biological and Therapeutic Significance","volume":"59","author":"Ediriweera","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological Functions of Autophagy Genes: A Disease Perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1080\/17512433.2020.1787829","article-title":"Copanlisib for the Treatment of Adults with Relapsed Follicular Lymphoma","volume":"13","author":"Magagnoli","year":"2020","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1093\/annonc\/mdw282","article-title":"First-in-Human Phase I Study of Copanlisib (BAY 80-6946), an Intravenous Pan-Class I Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors and Non-Hodgkin\u2019s Lymphomas","volume":"27","author":"Patnaik","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1182\/blood.V120.21.4853.4853","article-title":"Pharmacokinetics and Pharmacodynamics of IPI-145, a Potent Inhibitor of Phosphoinositide-3-Kinase-\u03b4,\u03b3, Following Single- and Multiple-Dose Administration in Healthy Subjects and Patients with Advanced Hematologic Malignancies","volume":"120","author":"Dunbar","year":"2012","journal-title":"Blood"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrclinonc.2018.28","article-title":"Targeting the PI3K Pathway in Cancer: Are We Making Headway?","volume":"15","author":"Janku","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/S1470-2045(21)00145-5","article-title":"Copanlisib plus Rituximab versus Placebo plus Rituximab in Patients with Relapsed Indolent Non-Hodgkin Lymphoma (CHRONOS-3): A Double-Blind, Randomised, Placebo-Controlled, Phase 3 Trial","volume":"22","author":"Matasar","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"13375","DOI":"10.1074\/jbc.273.22.13375","article-title":"The Tumor Suppressor, PTEN\/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate","volume":"273","author":"Maehama","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4108","DOI":"10.1158\/0008-5472.CAN-05-0124","article-title":"Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) Has Nuclear Localization Signal\u2013Like Sequences for Nuclear Import Mediated by Major Vault Protein","volume":"65","author":"Chung","year":"2005","journal-title":"Cancer Res."},{"key":"ref_135","first-page":"2124","article-title":"TEP1, Encoded by a Candidate Tumor Suppressor Locus, Is a Novel Protein Tyrosine Phosphatase Regulated by Transforming Growth Factor","volume":"57","author":"Li","year":"1997","journal-title":"Cancer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/onc.2009.384","article-title":"Suppression of Cellular Proliferation and Invasion by the Concerted Lipid and Protein Phosphatase Activities of PTEN","volume":"29","author":"Davidson","year":"2010","journal-title":"Oncogene"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1038\/ncb2874","article-title":"Deubiquitylation and Stabilization of PTEN by USP13","volume":"15","author":"Zhang","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/ncb3218","article-title":"Deubiquitylase OTUD3 Regulates PTEN Stability and Suppresses Tumorigenesis","volume":"17","author":"Yuan","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"7389","DOI":"10.1007\/s11033-012-1571-6","article-title":"Cell Cycle Arrest and Apoptosis by Expression of a Novel TPIP (TPIP-C2) CDNA Encoding a C2-Domain in HEK-293 Cells","volume":"39","author":"Mishra","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.snb.2019.01.080","article-title":"Near-Infrared-Light-Triggered Photoelectrochemical Biosensor for Detection of Alpha-Fetoprotein Based on Upconversion Nanophosphors","volume":"286","author":"Zhai","year":"2019","journal-title":"Sens. Actuators B Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1158\/0008-5472.CAN-13-2441","article-title":"Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell\u2013Cell Adhesion and Invasive Cell Migration in Human Breast Cancer","volume":"74","author":"Tokuda","year":"2014","journal-title":"Cancer Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.cellbi.2008.01.006","article-title":"PIKfyve: Partners, Significance, Debates and Paradoxes","volume":"32","author":"Shisheva","year":"2008","journal-title":"Cell Biol. Int."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1247\/csf.17003","article-title":"PI5P and PI(3,5)P2: Minor, but Essential Phosphoinositides","volume":"42","author":"Hasegawa","year":"2017","journal-title":"Cell Struct. Funct."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.18632\/oncotarget.26812","article-title":"Computational Analysis of Data from a Genome-Wide Screening Identifies New PARP1 Functional Interactors as Potential Therapeutic Targets","volume":"10","author":"Lodovichi","year":"2019","journal-title":"Oncotarget"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1182\/blood-2016-09-736892","article-title":"Identification of Apilimod as a First-in-Class PIKfyve Kinase Inhibitor for Treatment of B-Cell Non-Hodgkin Lymphoma","volume":"129","author":"Gayle","year":"2017","journal-title":"Blood"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.ajpath.2014.02.028","article-title":"Methuosis","volume":"184","author":"Maltese","year":"2014","journal-title":"Am. J. Pathol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/10\/1550\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:09:51Z","timestamp":1760130591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/10\/1550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,19]]},"references-count":146,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["biom13101550"],"URL":"https:\/\/doi.org\/10.3390\/biom13101550","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,19]]}}}