GPR68, also known as ovarian cancer G protein-coupled receptor 1 (OGR1), is a proton-sensing G-protein-coupled receptor (GPCR). It responds to extracellular acidity and is involved in multiple physiological processes. GPR68 can sense flow in endothelial cells, being essential for vascular physiology through flow-mediated dilation and outward remodeling [1]. It is also involved in cell survival-related pathways like the GPR68-ATF4 signaling in glioblastoma [2].

In gene-knockout models, Gpr68-deficient mice display impaired acute flow-mediated dilation and chronic flow-mediated outward remodeling in mesenteric arterioles, highlighting its crucial role in arteriolar endothelium and cardiovascular pathophysiology [1]. In glioblastoma, inhibition or knockdown of GPR68 using shRNA reduces cell survival in vitro and in zebrafish xenograft models by inducing ferroptosis [2,3]. In oral dysplasia, GPR68-deficient mice have a higher incidence of severe dysplasia or squamous cell carcinoma compared to wild-type mice, suggesting a protective role in tumorigenesis [4].

In conclusion, GPR68 is a multi-functional receptor involved in vascular physiology, cancer-related processes, and oral dysplasia. Gene-knockout mouse models have been instrumental in revealing its role in these biological processes and disease conditions, providing potential therapeutic targets for treating related diseases such as glioblastoma and understanding the mechanisms underlying oral tumorigenesis.