LGALS9 encodes galectin-9, a carbohydrate-binding protein with multifaceted immunoregulatory functions. As a ligand for the immune checkpoint molecule TIM-3, galectin-9 mediates Th1 cell apoptosis and suppresses T cell function 12. The protein is secreted via an ATG9A-dependent mechanism independent of classical autophagy 3. In pregnancy, galectin-9 plays a critical role in placental immunobiology. Trophoblast-derived galectin-9 activates CD11chigh decidual macrophages through CD44 binding, suppressing spiral artery remodeling—a process dysregulated in preeclampsia 4. Elevated circulating galectin-9 in early pregnancy predicts preeclampsia onset 4. During normal pregnancy, galectin-9 expression is enriched in tolerogenic immune cell subsets that colocalize at the maternal-fetal interface 5. In cancer contexts, galectin-9 expression is paradoxically downregulated by HPV-encoded circE7 in head and neck squamous cell carcinoma, promoting immune evasion and T cell exhaustion 6. Conversely, in glioblastoma, elevated galectin-9 contributes to immunosuppression by recruiting myeloid-derived suppressor cells and tumor-associated macrophages 7. Genetically, LGALS9 polymorphisms associate with rheumatoid arthritis susceptibility and disease manifestations in Chinese populations 8, and TIM-3-LGALS9 pathway dysregulation is implicated in multiple autoimmune diseases 2.