TEK (TEK receptor tyrosine kinase) is a cell-surface receptor tyrosine kinase that functions as the primary mediator of angiopoietin signaling in vascular biology. TEK binds angiopoietins (ANGPT1, ANGPT2, and ANGPT4) to regulate critical endothelial cell processes including angiogenesis, survival, migration, and adhesion [31108880]. The receptor operates through context-dependent signaling: in quiescent vessels, ANGPT1-TEK activation preferentially engages phosphatidylinositol 3-kinase and AKT cascades to promote vascular stability, while in migrating endothelial cells, it activates focal adhesion complexes and MAPK signaling to stimulate sprouting angiogenesis [31108880]. TEK expression increases during tumor angiogenesis, with stalk cells transitioning from high chemokine expression to elevated TEK as neovascularization progresses through angiogenic stages [38987599]. Beyond angiogenesis, TEK maintains vascular integrity and exerts anti-inflammatory effects by preventing leakage of plasma proteins and leukocytes from blood vessels [31108880]. Clinically, TEK is implicated in venous malformations through somatic gain-of-function mutations, which cause excessive signaling through the PI3K-AKT-mTOR pathway [38880808]. Recent studies reveal a PI3K-FOXO1-ANGPT-TEK feedforward circuit driving PIK3CA-related venous malformations, where PI3Kα hyperactivity amplifies upstream TIE2 receptor signaling [40410415]. TEK inhibition and ANGPT antagonism show promise as therapeutic targets for these previously intractable vascular anomalies [40410415].