GPR137 is an orphan G protein-coupled receptor that functions as a pro-oncogenic protein across multiple cancer types. Primary function: GPR137 promotes cancer cell proliferation, migration, and invasion through activation of distinct intracellular signaling pathways. 1 Mechanism: In ovarian cancer, GPR137 activates the Hedgehog pathway via RAB8A, which disassociates the GLI-SuFu protein complex, thereby promoting GLI nuclear translocation and pathway activation. 2 In other cancers, GPR137 regulates the PI3K/AKT pathway 3 and AMPK/AKT signaling. 4 GPR137 knockdown induces cell cycle arrest (typically G0/G1 or G2/M phase) and reduces epithelial-mesenchymal transition markers. 5 Disease relevance: GPR137 is significantly upregulated in prostate, 5 ovarian, 2 bladder, 6 gastric, 7 glioma, 8 and osteosarcoma tissues. 4 Clinical significance: GPR137 represents a potential therapeutic target for multiple cancers. Targeting GPR137 inhibits tumor growth in xenograft models and reduces metastatic potential, making it a candidate for novel cancer therapeutics. 5 2 3