DLL1 (Delta-like canonical Notch ligand 1) is a transmembrane ligand that activates Notch1, Notch2, and Notch3 receptors through cis and trans interactions 1. Following transinteraction, DLL1 undergoes clathrin-mediated endocytosis to promote Notch receptor extracellular domain transendocytosis, triggering NICD nuclear accumulation and Notch signaling [UniProt]. DLL1 is essential for embryonic development and adult stem cell maintenance across multiple tissues, mediating intercellular communication that regulates cell lineage specification, differentiation, and proliferation 2. In neural development, DLL1-Notch signaling regulates neuronal differentiation through lateral inhibition, controls neurogenesis in the neocortex, cerebellum, retina, and spinal cord, and maintains neural stem cell quiescence [UniProt]. DLL1 also plays critical roles in immune system development, promoting T cell and marginal zone B cell development while blocking B cell lineage differentiation 2. Additionally, DLL1 regulates myogenic progenitor pools, pancreatic cell proliferation, arterial identity maintenance, and intestinal secretory cell differentiation [UniProt]. Heterozygous DLL1 variants cause variable neurodevelopmental disorders characterized by intellectual disability, autism spectrum disorder, seizures, and brain malformations, supporting haploinsufficiency as a pathogenic mechanism 3. DLL1 has emerged as relevant in systemic vascular disease, aging immunity, and cancer immunity, suggesting therapeutic potential 4567.