The TEK receptor tyrosine kinase (TIE2) is expressed almost exclusively in endothelial cells in mice, rats, and humans. The TIE2 receptor possesses a unique extracellular domain containing 2 immunoglobulin-like loops separated by 3 epidermal growth factor-like repeats that are connected to 3 fibronectin type III-like repeats. The ligand for TIE2 is angiopoietin-1. Defects in TIE2 are associated with inherited venous malformations; the TIE2 signaling pathway appears to be critical for endothelial cell-smooth muscle cell communication in venous morphogenesis.