Delta-like canonical Notch ligand 4 (DLL4)

Delta-like canonical Notch ligand 4 (DLL4) is a single-pass transmembrane ligand for Notch receptors and is expressed primarily in arterial endothelial cells and other tissues undergoing active development or remodeling. DLL4 interacts with Notch receptors (NOTCH1, NOTCH4) to regulate cell differentiation, vessel branching, immune cell polarization, and tissue homeostasis. DLL4–Notch signaling is tightly regulated by stimuli such as VEGF, hypoxia, and cytokines, serving as a "brake" on angiogenic sprouting and tip cell formation, which is essential for balanced vascular development. Pathologically, DLL4 signaling contributes to cancer progression via tumor angiogenesis, to cardiometabolic disorders by promoting proinflammatory macrophage activation, and to retinal vascular diseases. Pharmacological inhibition of DLL4/Notch signaling shows therapeutic potential in inflammation and cancer but carries safety risks due to its role in normal vascular patterning, immune response, and developmental processes.

Other names

Delta-like protein 4Delta4Drosophila Delta homolog 4AOS6hdelta2DLL4delta 4delta ligand 4delta-like 4 homolognotch ligand DLL4notch ligand delta-2dll4UNQ1895/PRO4341

Inhibition of DLL4/Notch signaling (reducing angiogenesis, vessel branching, or inflammation); Blockade of DLL4–Notch binding (using antibodies); Inhibition of γ-secretase (prevents Notch receptor cleavage and activation)