Interestingly, some recent reports have described that a more profound and global GRK2 knockdown may be detrimental due to enhanced renin- and AT1R-mediated reactive oxygen species (ROS) production that can cause renal damage (Tutunea-Fatan et al., 2018) and the development of hypertension with age (Tutunea-Fatan et al., 2015). This evidence concerns the gene REN and hypertensive disorder.