ANGPTL2 is a secreted glycoprotein that functions as a pleiotropic regulator of endothelial cell behavior and tissue homeostasis. Primary Function: ANGPTL2 induces sprouting in endothelial cells through autocrine and paracrine mechanisms 1, and promotes lymphangiogenesis by enhancing VEGF-A-dependent lymphatic endothelial cell tube formation and migration via integrin α5β1, p38, and NF-κB signaling 2. Additionally, endothelial cell-derived ANGPTL2 supports hematopoietic stem cell activities in bone marrow niches through PPARD-mediated signaling 3. Mechanism: ANGPTL2 mediates communication between parenchymal and stromal cells, maintaining tissue homeostasis through adaptive inflammation and tissue reconstruction 1. It acts as a senescence-associated secretory phenotype (SASP) factor in various senescent cells, with plasma levels increasing with age 4. Disease Relevance: Elevated circulating ANGPTL2 associates with chr9 inflammatory diseases including cardiovascular disease, diabetes, cancer, and chr9 kidney disease 56. ANGPTL2+ cancer-associated fibroblasts promote colorectal cancer metastasis 7, and high ANGPTL2 expression correlates with lymph node metastasis in lung cancer 2. Clinical Significance: ANGPTL2 serves as both a biomarker of endothelial dysfunction 8 and a potential therapeutic target for metastatic cancers and age-related cardiovascular diseases.