Anxa4, a member of the Annexin family, is a calcium ion (Ca2+)- and phospholipid-binding protein [3,6,9]. It has potential roles in modulating membrane permeability, membrane trafficking, cellular growth, apoptosis, tumor invasion, and anti-tumor drug resistance [6,9]. It is involved in multiple signaling pathways such as the PI3K/Akt/eNOS pathway [1], JAK-STAT3 signaling [3], and Wnt-related GSK3β-Ikaros-ANXA4 signaling [4].

In preeclampsia, Anxa4 expression is downregulated. Overexpression of Anxa4 in trophoblast cells promotes cell proliferation and invasion, inhibits apoptosis via the PI3K/Akt/eNOS pathway, while knockdown has the opposite effects. In HBV-infected cells, Anxa4 is elevated and restricts HBV replication by inhibiting autophagic degradation of MCM2 [2]. In basal-like breast cancer, Anxa4 overexpression is associated with poor survival, and it activates JAK-STAT3 signaling by interacting with ANXA1 [3]. In high-glucose-induced fibroblast migration, GSK3β-Ikaros-ANXA4 signaling inhibits the process [4]. Pan-cancer analysis shows Anxa4 as a potential prognostic marker and therapeutic target in diverse cancer types [5]. In gastric cancer, circular RNA circ_0000592 promotes tumor progression by elevating ANXA4 expression via sponging miR-1179 [7]. In ovarian clear cell carcinoma, wild p53 activates Anxa4 transcription, promoting cell cycle progression and inhibiting apoptosis through the NF-κB signaling pathway [8].

In conclusion, Anxa4 plays crucial roles in various biological processes and disease conditions. Its functions in promoting trophoblast invasion in preeclampsia, restricting HBV replication, and influencing cancer progression, as revealed through functional studies, highlight its significance. These findings from different research models contribute to understanding disease mechanisms and may offer potential therapeutic targets in relevant diseases.