{"paper_id":"40924c08-81f5-488a-82ff-e34d818159d7","body_text":"Novel insights into the role of Annexin A2 signaling pathway in female reproductive system diseases: from mechanisms to advanced therapies\nPublication: American Journal of Physiology-Endocrinology and Metabolism\nArticles in Press\nAmerican Journal of Physiology-Endocrinology and Metabolism\nAbstract\nAnnexin A2 (ANXA2) is a calcium-dependent protein with high affinity for phospholipids, and its multifunctional nature has drawn increasing attention in the onset and progression of various disorders of the female reproductive system (FRS). Beyond its canonical roles in endocytosis, cytoskeletal dynamics, angiogenesis, and extracellular matrix (ECM) remodeling, ANXA2 signaling integrates phosphorylation events, interactions with S100A10, and fibrinolytic activity to shape reproductive biology. Emerging evidence demonstrates that aberrant ANXA2 expression is implicated in gynecological cancers, endometriosis, adenomyosis, infertility, and pregnancy-related complications, where it modulates processes such as epithelial–mesenchymal transition, trophoblast invasion, vascular integrity, and immune homeostasis. Elevated ANXA2 levels have been correlated with tumor aggressiveness, recurrence risk, chemoresistance, and poor prognosis, while circulating ANXA2 and exosome-derived ANXA2 show promise as minimally invasive biomarkers for benign reproductive system disorders. Despite these advances, the precise molecular mechanisms and context-specific functions of ANXA2 remain incompletely understood, and significant gaps persist regarding its clinical translation. This review synthesizes current knowledge of ANXA2 signaling in female reproductive diseases, highlights its potential diagnostic and therapeutic value, and identifies key challenges and research priorities. A deeper understanding of ANXA2 biology may not only refine disease stratification and prognosis but also open new avenues for targeted interventions, positioning ANXA2 as a promising node for precision medicine in reproductive health.\nFormats available\nYou can view the full content in the following formats:\nInformation & Authors\nInformation\nPublished In\nAmerican Journal of Physiology-Endocrinology and Metabolism\nArticles in Press\nCopyright\nCopyright © 2026 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0. Published by the American Physiological Society.\nHistory\nReceived: 21 October 2025\nRevised: 13 November 2025\nAccepted: 23 February 2026\nPublished online: 14 April 2026\nKeywords\nAuthors\nMetrics & Citations\nMetrics\nArticle Usage\n- For recently published articles, the total views count will show as 0 until a new month begins.\n- There is a 3–4 day delay in usage data reporting after article publication.\n- Citation counts are from the Crossref Cited-by service.\nAltmetrics\nDimensions\nScite\nCitations\nIf you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click on download.\nDownload article citation data for:\nAmerican Journal of Physiology-Endocrinology and Metabolism 0 0:0\nAmerican Journal of Physiology-Endocrinology and Metabolism 0 0:0\nView Options\nView options\nAccess content\nTo read the fulltext, please use one of the options below to sign in or purchase access.\nThis functionality works only for purchases made as a guest","source_license":"CC-BY-4.0","license_restricted":false}