{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:03:01Z","timestamp":1782975781895,"version":"3.54.5"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Lowe syndrome (LS) is an X-linked disorder caused by OCRL mutations, encoding a phosphatidylinositol 5-phosphatase. OCRL regulates phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    ]-dependent cytoskeletal dynamics and membrane trafficking in multiple cell types, including platelets. Clinically, LS manifests with cataracts, hypotonia, developmental delay, and progressive kidney disease. A subset of LS individuals shows bleeding tendency and occasional mild thrombocytopenia despite normal coagulation tests. Studies reveal impaired thrombus growth under flow, delayed platelet spreading on fibrinogen, abnormal clot retraction, and altered platelet formation with circulating barbell-shaped immature platelets, supporting a platelet dysfunction phenotype in LS, though exact molecular mechanisms remain undefined. Experimental studies suggest OCRL controls PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    pools required for coordinated actin and microtubule remodeling during platelet adhesion and thrombopoiesis. Pharmacological OCRL inhibition recapitulates defective spreading, persistent filopodia, actin nodules, and impaired marginal microtubule band depolymerization without major loss of GPIb-IX-V or \u03b1IIb\u03b23 receptors, supporting a signaling and cytoskeletal mechanism. Elevated plasma fibrinogen, VWF, and FVIII in LS may partially offset bleeding, though their contribution to the LS phenotype and relationship to vascular\/hepatic involvement remains unclear. Similarly, while the OCRL homolog INPP5B is abundant in platelets, its capacity to compensate for OCRL deficiency appears limited and requires further investigation. Recognition of this OCRL-dependent platelet phenotype has important clinical implications, including caution before surgical procedures and usage of medications that may worsen bleeding, highlighting the need for targeted diagnostic approaches and further mechanistic studies to improve the management of individuals with LS.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1886446","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:33:43Z","timestamp":1782970423000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bleeding and hemostatic defects in Lowe syndrome: the role of OCRL in platelets"],"prefix":"10.3389","volume":"14","author":[{"given":"Ana","family":"Bura","sequence":"first","affiliation":[{"name":"Faculty of Biotechnology and Drug Development, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonija","family":"Jurak Begonja","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology and Drug Development, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1681\/ASN.2010050565","article-title":"Mouse model for Lowe syndrome\/Dent Disease 2 renal tubulopathy","volume":"22","author":"Bothwell","year":"2011","journal-title":"J. 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