Delta-like non-canonical Notch ligand 2 (DLK2)

Delta-like non-canonical Notch ligand 2 (DLK2) is a single-pass transmembrane protein and member of the epidermal growth factor (EGF)-like superfamily, containing six EGF-like domains in its extracellular region and sharing high homology with DLK1[2][6]. DLK2 acts primarily as a non-canonical inhibitor of Notch signaling by binding the Notch1 receptor, functioning in cellular processes including regulation of adipocyte and chondrocyte differentiation, development, bone and fat homeostasis, and has been implicated in cancer cell proliferation and metastasis[2][4][6]. It exerts its functions both by direct modulation of Notch pathway activity and through interactions with signaling partners such as SYAP1 to activate the Akt pathway, thereby influencing osteoclastogenesis and bone metabolism[2][4]. DLK2's expression is widespread and dynamically regulated during development and in adult tissues, potentially acting in synergy or opposition to its homolog DLK1, fine-tuning differentiation across tissue types[2][4][6].

Other names

Protein delta homolog 2EGFL9UNQ2903/PRO28633EGF-like protein 9MGC2487Epidermal growth factor-like protein 9Delta-like 2 homolog

Non-canonical inhibition of Notch signaling via receptor binding; Modulation of Akt pathway via interaction with SYAP1; Modulation of cell differentiation and proliferation pathways