DLL3

DLL3 (Delta-like protein 3) is a protein encoded by the DLL3 gene in humans. It is a member of the Delta/Serrate/Lag-2 (DSL) family of Notch ligands. Unlike other ligands in this family, DLL3 is predominantly localized to the Golgi apparatus and intracellular compartments and is not widely presented on the cell surface. Through its intracellular localization, DLL3 can inhibit Notch signaling by interfering with the activity of canonical Notch receptor-ligand interactions.

During vertebrate development, DLL3 participates in somitogenesis and the segmentation clock by modulating Notch pathway activity. Proper expression of DLL3 is required for normal vertebral segmentation; disruption results in vertebral and rib malformations.

Mutations in DLL3 cause spondylocostal dysostosis type 1 (SCDO1), a congenital disorder characterized by abnormal segmentation of the axial skeleton, vertebral fusion, rib anomalies, scoliosis, and a short trunk. DLL3 mutations are inherited in an autosomal recessive pattern. In addition to developmental roles, DLL3 has been studied as a biomarker and therapeutic target in certain cancers, notably high-grade neuroendocrine tumors and small cell lung carcinoma, where DLL3 expression can be elevated and has been explored with targeted therapies in clinical trials.