DLL4 (Delta-like ligand 4) is a key Notch ligand involved in the regulation of vascular development and angiogenesis. It is predominantly expressed in endothelial cells and plays a crucial role in the formation and maintenance of arterial-venous identity during embryonic development. DLL4-mediated Notch signaling is essential for proper vascular morphogenesis, as evidenced by severe vascular defects in DLL4-deficient embryos. In addition to its developmental roles, DLL4 is implicated in various pathological conditions, including cancer. High expression of DLL4 has been observed in certain cancers, such as testicular and renal cancer, where it may contribute to tumor angiogenesis and progression. DLL4 also modulates macrophage function through the Notch signaling pathway, influencing immune responses and tissue repair. Recent studies have also highlighted the role of DLL4 in skeletal muscle, where it regulates muscle mass through interactions with Notch receptors in muscle cells. Overall, DLL4 is a critical regulator of Notch signaling in both physiological and pathological contexts, making it a potential target for therapeutic interventions.