Gpr52 is an orphan G protein-coupled receptor (GPCR) that is highly conserved and enriched in the brain. It is a Gs/olf-coupled receptor controlling various cyclic AMP (cAMP)-dependent physiological and pathological processes [1].

In a study using HdhQ140 mice, striatal knockdown of Gpr52 reduced mHTT levels, validating Gpr52 as a potential target for Huntington's disease (HD) [2]. In breast cancer research, knockout of Gpr52 in human triple-negative breast cancer (TNBC) cell lines and non-cancerous breast epithelial cell line MCF10A using CRISPR-Cas9 was associated with increased cell-cell interaction, altered 3D spheroid morphology, and increased invasion, suggesting a role in breast cancer progression [3].

In conclusion, Gpr52 plays a crucial role in cAMP-dependent physiological and pathological processes. The gene knockout models in mice and cell lines have revealed its potential as a therapeutic target in diseases such as Huntington's disease and breast cancer, providing insights into its function in these disease conditions.

References:

1. Ali, Saghir, Wang, Pingyuan, Murphy, Ryan E, Allen, John A, Zhou, Jia. 2024. Orphan GPR52 as an emerging neurotherapeutic target. In Drug discovery today, 29, 103922. doi:10.1016/j.drudis.2024.103922. https://pubmed.ncbi.nlm.nih.gov/38387741/

2. Wang, Congcong, Zhang, Yu-Fang, Guo, Shimeng, Lu, Boxun, Hu, Youhong. 2020. GPR52 Antagonist Reduces Huntingtin Levels and Ameliorates Huntington's Disease-Related Phenotypes. In Journal of medicinal chemistry, 64, 941-957. doi:10.1021/acs.jmedchem.0c01133. https://pubmed.ncbi.nlm.nih.gov/33185430/

3. Hanif, Sarah Z, Au, CheukMan Cherie, Torregroza, Ingrid, Hébert, Terence E, Brown, Kristy A. 2024. The Orphan G Protein-Coupled Receptor GPR52 is a Novel Regulator of Breast Cancer Multicellular Organization. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.07.22.604482. https://pubmed.ncbi.nlm.nih.gov/39091857/