GPR52 is a highly conserved, brain-enriched, G-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.

中文翻译：

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孤儿 GPR52 作为新兴神经治疗靶点

GPR52 是一种高度保守、脑部富集的 G 偶联孤儿 G 蛋白偶联受体 (GPCR)，可控制各种环 AMP (cAMP) 依赖性生理和病理过程。刺激GPR52活性可能有益于精神分裂症、精神疾病和其他人类神经系统疾病的治疗，而抑制其活性可能为亨廷顿病提供潜在的治疗方法。令人兴奋的是，HTL0048149 (HTL'149) 是一种口服 GPR52 激动剂，已进入治疗精神分裂症的 I 期人体临床试验。在这篇简明的综述中，我们总结了目前对 GPR52 受体分布及其结构和功能的理解，重点介绍了小分子 GPR52 配体药物发现工作的最新进展。还简要讨论了针对 GPR52 的新型疗法所带来的机遇和挑战。