TIE1 is a transmembrane receptor tyrosine kinase that plays crucial roles in vascular development and disease through multiple mechanisms. As part of the angiopoietin-Tie signaling system, TIE1 modulates angiogenesis and lymphangiogenesis by regulating TIE2 activity and VEGFR3 cell-surface expression 1. The protein facilitates heterodimerization with TIE2, and disruption of this interaction affects vascular signaling pathways 2. TIE1 has been identified as a receptor for LECT2, where binding interrupts TIE1/TIE2 heterodimerization and promotes TIE2 homodimerization, ultimately inhibiting endothelial cell migration and tube formation 2. In lymphatic vessels, TIE1 is essential for VEGF-C-induced lymphangiogenesis through Ang2/Tie/PI3K signaling pathways that regulate VEGFR3 presentation 1. Clinically, TIE1 dysfunction is associated with lymphatic malformation 11, and mutations affect lymphatic vessel development 1. The protein also demonstrates oncogenic properties in cervical cancer, where it promotes tumor progression through interaction with Basigin and activation of matrix metalloproteinase pathways 3. Additionally, TIE1 has been implicated as a potential therapeutic target for ADHD based on proteomic analyses 4. These findings establish TIE1 as a critical regulator of vascular homeostasis with significant clinical implications.