In this regard, the G protein-coupled receptor kinase 2 (GRK2) can act as regulator of both G protein-coupled receptors (GPCRs), including CXCR4/ACKR3, and GFR of the receptor tyrosine kinase (RTKs) family, and has emerged as a critical signaling hub involved in orchestrating most tumor hallmarks [21,22,23]. This evidence concerns the gene RAPGEF5 and neoplasm.