GPR85 (SREB2) is a brain-enriched orphan G protein-coupled receptor located on human chromosome 7 1 that functions as a negative regulator of hippocampal adult neurogenesis and associated cognitive processes 2. The receptor is highly evolutionarily conserved across vertebrates 3 and shows predominant expression in the hippocampal dentate gyrus and other brain structures characterized by high neuroplasticity 3. GPR85 interacts with the postsynaptic density protein PSD-95 through its C-terminal PDZ-binding motif, positioning it within synaptic scaffolding complexes 4. Phylogenetic analysis suggests GPR85 may bind ATP, ADP, and UDP glucose 5. Functionally, GPR85 negatively regulates new neuron proliferation and survival in the dentate gyrus, with transgenic overexpression reducing cognitive performance in spatial discrimination and working memory tasks 2. GPR85 dysfunction is implicated in multiple CNS disorders, particularly schizophrenia 6 and autism spectrum disorder, where missense mutations cause aberrant receptor accumulation, endoplasmic reticulum stress, and impaired dendrite formation 4. Recent evidence also associates GPR85 with pain mechanisms 7. The receptor represents a promising therapeutic target for treating cognitive symptoms in psychiatric disorders through modulation of hippocampal neurogenesis.