Adgrl4, also known as ELTD1, is an adhesion G protein-coupled receptor (aGPCR) [1]. It plays significant roles in regulating physiological and tumour angiogenesis [3]. It may be involved in pathways such as Notch signalling, as its silencing in endothelial cells affects genes related to this pathway like DLL4, JAG1 and HES2 [3]. It is also associated with cell metabolism, as its silencing induces the expression of ACLY and SLC25A1 [3].

In breast cancer models, tumours expressing recombinant murine Eltd1 grew faster, had enhanced metastatic ability, and created an immunosuppressive microenvironment with increased M2-like macrophages and PD-L1 expression [2]. In neuroblastoma, knockdown of Adgrl4 inhibited cell growth, aggressiveness, EMT, and angiogenesis by inactivating the ERK/STAT3 signalling pathway [4]. In clear cell renal cell carcinoma, ADGRL4+ renal tubule cells had highly metastatic and angiogenesis-inducing characteristics, and more of these cells indicated a worse survival [5].

In summary, Adgrl4 is crucial in angiogenesis, tumour growth, metastasis, and creating an immunosuppressive microenvironment in cancer. Studies using gene knockdown in cell lines and animal models, like in breast and neuroblastoma cancers, have revealed its role in promoting tumour-related processes, providing insights into potential therapeutic targets for these diseases [2,4].