ANXA6 is a calcium-dependent membrane-binding protein that functions as a multifactorial scaffolding protein involved in cellular cholesterol homeostasis and intracellular signaling. It regulates calcium release from intracellular stores and may associate with CD21. At the molecular level, ANXA6 organizes membrane domains, recruits signaling regulators including p120GAP and PKC, and modulates endocytic and exocytic transport through interactions with the actin cytoskeleton 1. In cancer contexts, ANXA6 exhibits complex, often opposing roles depending on cancer type. In nasopharyngeal carcinoma, ANXA6 downregulation correlates with poor survival and increased metastasis, with overexpression linked to better immunotherapy response 2. Similarly, in prostate cancer and triple-negative breast cancer, higher ANXA6 expression associates with tumor suppression and improved survival, promoting CD4+ and CD8+ T cell chemotaxis and M1 macrophage polarization 3 4. Conversely, in breast cancer chemotherapy contexts, ANXA6-enriched extracellular vesicles promote metastatic niche formation in lung tissue via NF-κB-dependent endothelial activation and CCL2-mediated monocyte recruitment 5. AnxA6 SUMOylation at specific lysine residues enhances its tumor-suppressive capacity by facilitating EGFR-PKCα complex formation, suppressing EGFR-ERK signaling and increasing gefitinib sensitivity in epithelial cancers 6 and cisplatin sensitivity in bladder cancer 7. In acute ischemic stroke, ANXA6 overexpression reduces infarction volume and promotes synaptic plasticity 8. Recent evidence suggests ANXA6 dysregulation in recurrent spontaneous abortion through macrophage pyroptosis and inflammatory activation via the NF-κB pathway 9.