Annexin A1, Annexin A2, Annexin A3, Annexin A4, and Annexin A5 (ANXA1-A5)

The Annexin A family (A1–A5) comprises a group of calcium-dependent phospholipid-binding proteins that are critical regulators of inflammation, coagulation, and cellular signaling (NIH, 2023). Annexin A1 (ANXA1) is a key mediator of the anti-inflammatory actions of glucocorticoids, functioning by inhibiting phospholipase A2 and signaling through the FPR2/ALX receptor to promote the resolution of inflammation (Wikipedia, 2024). Annexin A2 (ANXA2) acts as a cell surface receptor for tissue plasminogen activator (tPA) and plasminogen, playing a significant role in fibrinolysis and being frequently overexpressed in various cancers where it promotes invasion and metastasis (NIH, 2019). Annexin A5 (ANXA5) is distinguished by its high affinity for phosphatidylserine, which allows it to act as an endogenous anticoagulant and serves as a widely used biomarker for imaging apoptotic cells in vivo (MDPI, 2024). Annexins A3 and A4 are also involved in specialized processes such as neutrophil function and cancer drug resistance, respectively (Frontiers, 2025). Interacting drugs include glucocorticoids like dexamethasone, which induce ANXA1 expression, and recombinant human Annexin A5, which is being developed for its anticoagulant and anti-inflammatory properties (Frontiers, 2025). Due to their diverse roles in disease pathogenesis, these proteins are actively investigated as therapeutic targets and diagnostic markers in oncology, cardiovascular medicine, and chronic inflammatory disorders (NIH, 2023).

Other names

Lipocortin 1MacrocortinCalpactin IILipocortin 2Calpactin Ip36Placental anticoagulant protein IVLipocortin 3PAP-IIILipocortin 4PAP-IIEndonexin ILipocortin 5PAP-IAnnexin VAnchorin CII

Annexin A1 is induced by glucocorticoids and acts as an agonist for the Formyl Peptide Receptor 2 (FPR2/ALX) to inhibit phospholipase A2 and NF-κB signaling (NIH, 2024). Annexin A2 functions as a co-receptor for tPA and plasminogen, promoting plasmin generation (NIH, 2019). Annexin A5 binds to phosphatidylserine on cell membranes, shielding it from procoagulant factors and serving as a marker for apoptosis (MDPI, 2024).