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Annexin A5 (ANXA5) is a member of the annexin family of calcium-dependent phospholipid-binding proteins. Its canonical function is to bind with high affinity to phosphatidylserine (PS) on the plasma membrane—especially when exposed during apoptosis—making it a key marker for apoptotic cell detection. In the coagulation cascade, annexin A5 acts as an indirect anticoagulant by forming a shield on PS-rich membranes, thereby inhibiting access of coagulation factors and downregulating thrombin generation. It participates in diverse physiological and pathological processes including signal transduction, vesicle trafficking, membrane repair, bone and cartilage mineralization, anti-inflammatory, antithrombotic, and neuroprotective roles. Autoantibodies against annexin A5 are implicated in antiphospholipid syndrome—a thrombophilic disorder associated with recurrent pregnancy loss and vascular thrombosis. Recombinant annexin A5 is widely used in laboratory diagnostics, especially as a probe for apoptosis. Although prominent as a biomarker/reagent, there are no approved direct drugs targeting ANXA5; its high affinity and specific biochemical actions, however, have been explored experimentally for drug delivery and imaging applications[1][2][3][4][5][6].
Binds to exposed phosphatidylserine on cell surfaces in a calcium-dependent manner, shielding negatively charged phospholipids and inhibiting coagulation cascade (by blocking access to coagulation factors such as prothrombin)[5][3][2]. Inhibits apoptosis or signals apoptosis detection (by binding to PS externalized on apoptotic cells)[3][6]. Indirect antithrombotic activity (prevents formation of procoagulant complexes)[2][3][5]. Inhibits phospholipase A1 (protects membrane integrity)[3]. Modulates mineralization in bone and cartilage by enhancing calcium influx and hydroxyapatite deposition[2].
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