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Review
. 2025 Apr 26:18:5655-5672.
doi: 10.2147/JIR.S511439. eCollection 2025.

Annexin A: Cell Death, Inflammation, and Translational Medicine

Zibing Qian  1 , Ziyi Li  1 , Xuebin Peng  2 , Yongwu Mao  2 , Xiaorong Mao  1   2 , Junfeng Li  1   3
Affiliations
Review

Annexin A: Cell Death, Inflammation, and Translational Medicine

Zibing Qian et al. J Inflamm Res. .

Abstract

The annexin superfamily proteins, a family of calcium-dependent phospholipid-binding proteins, are involved in a variety of Ca²+-regulated membrane events. Annexin A, expressed in vertebrates, has been implicated in a variety of regulated cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, ferroptosis, and neutrophil extracellular trap-induced cell death (NETosis). Given that inflammation is a key driver of cell death, the roles of Annexin A in inflammation have been extensively studied. In this review, we discuss the regulatory roles of Annexin A in RCD and inflammation, the development of related targeted therapies in translational medicine, and the application of animal models to study these processes. We also analyze current challenges and discuss future directions for improved diagnostic and therapeutic strategies.

Keywords: Annexin A; inflammation; regulated cell death; translational medicine.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Annexin A regulates regulated cell death patterns such as autophagy, ferroptosis, and pyroptosis. Annexin A1 activates the PI3K/AKT signaling pathway, leading to inhibition of autophagy. Annexin A2 regulates autophagy flow by blocking AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) pathways. Annexin A5 and A6 play a role in the fusion of autophagosomes with lysosomes. Knockdown Annexin A10 inhibits autophagy mediated TFRC degradation induced ferroptosis. p-STAT3 promotes Annexin A2 expression at the transcriptional level, thereby activating caspase-1 to mediate pyroptosis. Annexin A2 promotes NLRP3 inflammasome activation through Atg5-dependent autophagy, ultimately leading to pyroptosis. Annexin A7 decreases autophagy-induced NLRP3 inflammasome-mediated pyroptosis in epithelial cells. Annexin A3 can inhibit pyroptosis via the NLRC4/AIM2 axis.
Figure 2
Figure 2
The principle of apoptosis detection using Annexin A5 probes.
Figure 3
Figure 3
Overview of diseases associated with changes in annexin expression levels.
See this image and copyright information in PMC

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