GPR17 in Glioblastoma: Structure, Ligand Interactions, and Therapeutic Targeting

G protein-coupled receptor 17 (GPR17) is a crucial protein encoded by the GPR17 gene, which belongs to the G protein-coupled receptor (GPCR) family. It serves a pivotal function in cellular responses to various stimuli. GPR17 is found in various organs, including the brain, spinal cord, kidneys, liver, and immune cells. It is especially prevalent in oligodendrocytes, underscoring its significance in myelination. GPR17 is involved in myelination, inflammation, and neuroprotection. Recent studies highlight the therapeutic potential of targeting GPR17 in glioblastoma, a highly aggressive brain cancer, as it is overexpressed in tumor tissues and plays a critical role in tumor progression and invasion. Understanding the structure of GPR17 and its interactions with ligands and functional signaling pathways is crucial for developing targeted therapeutics for conditions involving myelin degradation, neuroinflammation, and immune dysregulation. To guide this exploration, this review is organized into distinct sections covering the sequence and structural features of GPR17, its natural and synthetic ligands, its role in glioblastoma progression, its associated signaling pathways, and the potential of using GPR17 as a therapeutic target. Each section in the review consolidates current findings to offer an integrated view of GPR17 biology and its translational relevance in oncology.