Orphan GPR52 as an emerging neurotherapeutic target

Saghir Ali, Pingyuan Wang, Ryan E. Murphy, John A. Allen, Jia Zhou

Research output: Contribution to journalReview articlepeer-review


GPR52 is a highly conserved, brain-enriched, Gs/olf-coupled orphan G protein-coupled receptor (GPCR) that controls various cyclic AMP (cAMP)-dependent physiological and pathological processes. Stimulation of GPR52 activity might be beneficial for the treatment of schizophrenia, psychiatric disorders and other human neurological diseases, whereas inhibition of its activity might provide a potential therapeutic approach for Huntington's disease. Excitingly, HTL0048149 (HTL’149), an orally available GPR52 agonist, has been advanced into phase I human clinical trials for the treatment of schizophrenia. In this concise review, we summarize the current understanding of GPR52 receptor distribution as well as its structure and functions, highlighting the recent advances in drug discovery efforts towards small-molecule GPR52 ligands. The opportunities and challenges presented by targeting GPR52 for novel therapeutics are also briefly discussed.

Original languageEnglish (US)
Article number103922
JournalDrug Discovery Today
Issue number4
StatePublished - Apr 2024


  • GPR52
  • Huntington's disease
  • agonists
  • central nervous system disorders
  • drug discovery
  • orphan GPCR
  • schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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