Adhesion G protein-coupled receptor L4 (ADGRL4)

Adhesion G protein-coupled receptor L4 (ADGRL4), also known as ELTD1, is an orphan adhesion G protein-coupled receptor predominantly expressed in endothelial cells and vascular smooth muscle, where it serves as a critical modulator of angiogenesis and vascular remodeling[1][3][4][5]. ADGRL4 regulates endothelial cell behavior and vessel formation both physiologically and in response to tumor development, and is upregulated by VEGF and downregulated by DLL4[4][5]. It is markedly increased in tumor-associated endothelium in several cancers—including glioblastoma, colorectal, renal, ovarian, breast, and head and neck—where its expression correlates with altered vessel morphology, invasion, metastasis, and, in some contexts, improved response to therapy[1][3][4][5]. Experimental inhibition (siRNA or antibodies) impairs endothelial sprouting and tumor growth without major systemic toxicity in preclinical models, making ADGRL4 an attractive, but complex, oncology target[1][3][5]. The precise molecular mechanism is not fully delineated: canonical GPCR signaling has not been observed, and ADGRL4 appears to regulate distinctive transcriptional and metabolic networks involved in vessel development and differentiation[4][5]. No approved drugs are currently known to target ADGRL4 directly, but its expression is already used as a potential biomarker for prognosis and therapy monitoring in certain cancers[3][5].

Other names

ELTD1ETLEGF latrophilin and seven transmembrane domain-containing protein 1EGF-TM7-latrophilin-related proteinUNQ202/PRO228KPG_003

Inhibition leads to impaired angiogenesis, reduced tumor growth, and improved survival in preclinical cancer models (antibody and RNAi approaches)