MEOX2 is a mesodermal homeobox transcription factor with context-dependent roles in development and disease. During normal development, it regulates somitogenesis and limb muscle differentiation 1. In vascular biology, MEOX2 acts as a negative regulator of angiogenesis by activating the cell cycle inhibitors CDKN1A and CDKN2A in endothelial cells, thereby suppressing vascular cell proliferation 2. However, MEOX2 exhibits markedly different oncogenic functions in multiple cancers. In glioblastoma, MEOX2 promotes classical glioblastoma stem cell proliferation and stemness maintenance through NOTCH signaling and mediates resistance to macrophage phagocytosis 3. MEOX2 enhances ERK signaling in glioblastoma through a feed-forward mechanism and cooperates with p53 and PTEN loss to drive proliferation 4. MEOX2 also regulates Cathepsin S to promote glioma cell proliferation and motility 5, and interacts with PARP1 to enhance DNA repair and chemotherapy resistance 6. In lung cancer, the MEOX2/GLI1 axis promotes EGFR overexpression through epigenetic mechanisms and confers resistance to EGFR-TKI and cisplatin therapies 7. Similarly, in ovarian cancer, elevated MEOX2 expression associates with cisplatin resistance by activating E2F target and DNA repair pathways 8. These findings establish MEOX2 as a therapeutic target in multiple malignancies.