ANXA8 (annexin A8) is a calcium and phospholipid-binding protein that plays critical roles in cellular regulation and disease pathogenesis. The protein functions as a key regulator of cell phenotype maintenance, particularly in epithelial cells, where downregulation is both necessary and sufficient for neuronal transdifferentiation of retinal pigment epithelial cells 1. ANXA8 modulates cellular signaling pathways through its involvement in EGF receptor trafficking and signaling, working alongside other annexins to fine-tune EGFR activity 2. The protein's expression is regulated by epigenetic mechanisms, with CpG methylation controlling its tissue-specific expression patterns 3. In disease contexts, ANXA8 demonstrates opposing roles depending on the pathological setting. In atherosclerosis, ANXA8 promotes disease progression by enhancing endothelial-leukocyte interactions and platelet adhesion, with deficiency leading to reduced atherosclerotic burden 4. Conversely, in cancer, ANXA8 can have complex effects: it promotes cell viability and invasion in pancreatic cancer through HIF-1α activation 3, facilitates non-small cell lung cancer progression via the RBM15-mediated m6A modification pathway 5, and serves as a prognostic marker in renal cell carcinoma where it influences cell cycle regulation 6. However, in cholangiocarcinoma, ANXA8 downregulation promotes metastasis through EGF-FOXO4 signaling and epithelial-to-mesenchymal transition 7.