The adhesion G protein-coupled receptor Gpr56 is implicated in diverse biological processes; however, its function in the kidney remains largely undefined. We previously reported that Gpr56 is ubiquitously expressed along the renal tubules—specifically in the proximal tubule, loop of Henle, and collecting duct—but is absent in glomeruli. We further established a whole kidney-specific knockout mouse model (Gpr56KS-KO) using the Pax8-Cre driver and demonstrated that these mice exhibit normal development and baseline renal homeostasis, with no significant alterations in urine biochemistry, blood electrolytes, or glomerular filtration rate (GFR) compared to controls. Here, we investigated the physiological role of Gpr56 in the context of renal injury. Control and Gpr56KS-KO mice were subjected to an adenine challenge (50 mg/kg, i.p., 10 days). In baseline, GFR was comparable between control and Gpr56KS-KO in both male (1205±114 vs 1245±108 ml/min/100 g BW, NS) and female (1191±107 vs 1163±78 ml/min/100 g BW, NS) mice. Following adenine treatment, both genotypes exhibited a significant decline in GFR compared to baseline. However, the functional deficit was significantly more severe in the knockout group. Post-treatment GFR was significantly lower in Gpr56KS-KO mice compared to controls in both males (300±90 vs 599±170 ml/min/100 g BW, P 4-fold, P 5-fold, P < 0.01). Collectively, these findings demonstrate that Gpr56 confers a protective benefit against adenine-induced renal injury in both sexes. Future studies will define the underlying mechanisms and evaluate Gpr56 as a potential therapeutic target for kidney diseases. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Xue et al. (Fri,) studied this question.