This work revealed ADGRL4/ELTD1 to be upregulated in tumour-associated endothelial cells and vascular smooth muscle cells (head and neck, renal, colorectal and ovarian cancers) and to be essential for sprouting angiogenesis in both zebrafish and humans as well as being regulated by two key angiogenic ligands, namely upregulation by vascular endothelial growth factor (VEGF), and downregulation by the Notch ligand delta-like ligand 4 (DLL4). Here, VEGFA is linked to ovarian carcinoma.