GPR88 is an orphan G protein-coupled receptor predominantly expressed in the brain, particularly in the striatum, that plays crucial roles in cognitive function, motor control, and emotional processing 1. The receptor couples to Gi/o signaling pathways and demonstrates constitutive activity 2. GPR88 functions as a negative regulator of other GPCR signaling, inhibiting both μ-opioid receptor and kappa-opioid receptor (KOR) responses through direct protein-protein interactions 3. This inhibitory function appears particularly important in dopamine D1-receptor-containing neurons of the basal ganglia direct pathway 3. Disease relevance includes associations with childhood-onset chorea with psychomotor retardation, where GPR88 mutations are among the genetic causes 4. The receptor is also implicated in various neuropsychiatric disorders including schizophrenia, Parkinson's disease, anxiety, and addiction 15. Additionally, GPR88 has emerged as a potential biomarker in metabolic associated steatotic liver disease 6. Despite its therapeutic potential as a neurotherapeutic target, effective synthetic ligands remain under development, with recent compounds like BI-9508 showing promise as research tools 7. The receptor's brain-specific expression profile and involvement in multiple CNS disorders make it an attractive target for novel therapeutic development.