Gpr87, a G protein-coupled seven-transmembrane receptor, was first described as an orphan receptor in 2001. Despite its homology to P2Y receptors, its endogenous ligands remain uncertain, with lysophosphatidic acid being a proposed but unconfirmed ligand [4]. Gpr87 is involved in multiple biological processes and signaling pathways, potentially playing a role in the development and progression of various diseases [4].

In renal fibrosis, tubule-specific Gpr87 deletion in unilateral ureteral obstruction (UUO) mice dramatically ameliorated tubulointerstitial fibrosis. Gpr87 accelerated glycolysis and mitochondrial injury via YAP-hexokinase-2 signaling, promoting renal fibrosis [1]. In lung adenocarcinoma, Gpr87 silencing reduced cell invasion and migration, and Gpr87 expression was positively correlated with immune infiltration and associated with immune and chemotherapy resistance [2]. In A431 cells, knockdown of Gpr87 using siRNA significantly reduced lysophosphatidic acid-induced colony dispersal, suggesting Gpr87 acts as an LPA receptor and induces colony dispersal via EGFR transactivation [3].

In conclusion, Gpr87 is implicated in multiple disease-related processes. Gene-knockout (KO) or conditional-knockout (CKO) mouse models, like in the study of renal fibrosis, have been crucial in revealing its role in promoting disease progression. Its functions in accelerating glycolysis and mitochondrial injury in renal fibrosis, promoting tumor cell invasion in lung adenocarcinoma, and mediating cell-colony dispersal highlight its importance as a potential therapeutic target in these disease areas.