GPR17 Gene: Function, Expression, and Disease Associations

GPR17 is a G protein-coupled receptor that responds to both uracil nucleotides (e.g., UDP, UDP-glucose) and cysteinyl-leukotrienes (e.g., LTD4). It is primarily expressed in the central nervous system, particularly in oligodendrocyte precursor cells, and plays a critical role in oligodendrocyte differentiation and myelination. GPR17 is also involved in inflammatory responses and has been implicated in brain injury, multiple sclerosis, and certain cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• GPCR downstream signaling (cAMP inhibition)

• UDP-glucose signaling

• Cysteinyl-leukotriene signaling

• Oligodendrocyte differentiation and myelination

GPR17 is a 367-amino acid integral membrane protein with seven transmembrane domains, characteristic of class A G protein-coupled receptors. It is activated by both uracil nucleotides (UDP, UDP-glucose) and cysteinyl-leukotrienes (LTD4, LTC4), coupling primarily to Gi/o proteins to inhibit adenylyl cyclase. The receptor is highly expressed in oligodendrocyte precursor cells and is essential for their timely differentiation into myelinating oligodendrocytes. In the injured brain, GPR17 is upregulated in reactive astrocytes and microglia, contributing to neuroinflammation and delayed repair. Its dual ligand specificity and restricted expression pattern make it a promising therapeutic target for demyelinating diseases and brain injury.