LYPD3 is a highly glycosylated cell surface protein that functions as a tumor-promoting factor across multiple cancer types. Mechanistically, LYPD3 supports cell migration and invasion, with its glycosylation modulating subcellular localization and anti-metastatic activity 1. In lung adenocarcinoma, LYPD3 expression is elevated and positively correlated with tumor stage and poor survival outcomes 2. LYPD3 regulates malignant phenotypes through multiple pathways: the JUP/AGR2/LYPD3 axis maintains melanoma stemness and promotes glycolysis 3, while LYPD3 can be targeted by miR-151-5p in head and neck cancer to suppress metastasis 1. In lung cancer, LYPD3 associates with immune cell infiltration and altered immunotherapy response 4, and serves as a coefficient factor in pyrimidine metabolism-related prognostic signatures 5. LYPD3 expression is regulated by DNA methylation in its promoter region 2. Additionally, LYPD3 protects vascular smooth muscle cells from apoptosis in abdominal aortic aneurysm through a circCBFB/miR-28-5p regulatory axis 6. In breast cancer, the FOXA1/GRHL2-regulated LYPD3/AGR2 pathway drives endocrine therapy resistance, and blocking LYPD3 or AGR2 inhibits resistant tumor growth 7. These findings establish LYPD3 as a multifunctional oncogenic protein with prognostic and therapeutic significance.