Gpr87, a G protein-coupled seven-transmembrane receptor, was first described as an orphan receptor in 2001. Despite its high structural homology to some extracellular nucleotide-activated P2Y receptors, its endogenous ligands remain uncertain. It is involved in multiple biological processes and associated with various signaling pathways [3].

In renal fibrosis, tubule-specific GPR87 deletion in UUO mice dramatically ameliorated tubulointerstitial fibrosis. GPR87 was found to accelerate glycolysis and mitochondrial injury by YAP-hexokinase-2 signaling, promoting renal fibrosis [1]. In lung adenocarcinoma, GPR87 silencing reduced cell invasion and migration. High GPR87 expression predicts poor survival in patients. It promotes metastasis through the AKT-eNOS-NO axis [2,4]. In esophageal squamous cell carcinoma, GPR87 overexpression increased cell viability, invasion, proliferation, and angiogenesis, while knockdown suppressed tumor growth. It regulates VEGFA expression via STAT3 activation [5]. In pancreatic ductal adenocarcinoma, GPR87 promoted the expansion of stem cells by forming a positive feedback loop with JAK2 and STAT3 [6].

In conclusion, Gpr87 plays crucial roles in multiple disease conditions, especially in promoting fibrosis and cancer progression. The use of gene knockout or conditional knockout mouse models has been instrumental in revealing these functions, providing potential therapeutic targets for diseases such as chronic kidney disease, lung adenocarcinoma, esophageal squamous cell carcinoma, and pancreatic ductal adenocarcinoma.