ANGPT4 is a secreted ligand that binds to and activates the TEK/TIE2 receptor tyrosine kinase, modulating angiopoietin signaling to promote endothelial cell survival, migration, and angiogenesis 1. In normal physiology, ANGPT4 plays critical roles in tissue regeneration and repair: it initiates a signaling cascade during cardiac regeneration through the Tie2-MAPK pathway, promoting cardiomyocyte proliferation and scar resolution 2. ANGPT4 also supports osteogenesis-angiogenesis coupling in bone repair, with expression upregulated in melatonin-treated bone marrow mesenchymal stem cells 3. In pathological contexts, ANGPT4 overexpression promotes tumor progression across multiple cancer types including lung adenocarcinoma, glioblastoma, and ovarian cancer by enhancing endothelial proliferation, tumor vascular expansion, and downstream ERK1/2 and PI3K/AKT signaling 1, 4. ANGPT4 also reshapes the tumor immune microenvironment toward immune evasion 5. Disease associations include linkage to mixed Alzheimer's disease and vascular dementia 6, and genome-wide association with depressive symptoms in older adults 7. ANGPT4 inhibition represents a potential therapeutic strategy for cancer treatment, while ANGPT4 augmentation shows promise for cardiac and bone regeneration.