DLK1 (delta-like non-canonical Notch ligand 1) is a membrane-bound protein that regulates multiple developmental processes through inhibition of TGF-β superfamily signaling rather than canonical Notch pathways. DLK1 directly binds to and antagonizes Activin receptor type 2B (ACVR2B), competing with canonical TGF-β ligands to inhibit downstream signaling 1. This mechanism promotes myoblast differentiation by blocking Myostatin-ACVR2B signaling and interferes with SMAD2/3-NICD complex formation, indirectly affecting Notch signaling 1. DLK1 plays critical roles in human development and disease, with haploinsufficiency causing variable neurodevelopmental disorders including intellectual disability, autism spectrum disorder, and brain malformations 2. Mutations in DLK1 are associated with central precocious puberty 3, and paternal deletions encompassing DLK1 cause Temple syndrome characterized by growth delays and precocious puberty 4. In cancer contexts, DLK1 shows high expression in multiple solid tumors including neuroblastoma and adrenocortical carcinoma, where it regulates tumor cell plasticity and chemoresistance 56. DLK1-targeting antibody-drug conjugates demonstrate therapeutic potential in DLK1-expressing cancers 56. Additionally, DLK1 serves as a marker for adipose stem cell populations, with DLK1-negative cells showing enhanced proliferative and adipogenic capacity 7.