Advances in Dynamic Regulation of GPER Subcellular Localization and Biological Functions: from Molecular Mechanisms to Therapeutic Targets

HUANG Xianming¹, ZHOU Yutao², LIU Jing³, CHEN Huijuan⁴, LIU Liyan⁵, YU Tenghua⁶, XIONG Meixue⁷*

(¹Department of Pathology, Jiangxi Cancer Hospitals & Institute, Nanchang 330029, China; ²School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China; ³School of Pharmacy, Nanchang University, Nanchang 330006, China; ⁴Department of Oncology, the First Hospital of Nanchang, Nanchang 330008, China; ⁵Pharmacy Department, Jiangxi Cancer Hospitals & Institute, Nanchang 330029, China; ⁶Department of Breast Tumor Surgery, Jiangxi Cancer Hospitals & Institute, Nanchang 330029, China; ⁷Department of General Surgery, the People’s Hospital of Gongqing City, Jiujiang 332020, China)

Abstract:

The GPER (G protein-coupled estrogen receptor) has garnered significant attention in biomedical research as a novel estrogen receptor in recent years. Its unique intracellular localization not only enables it to play a vital role in cellular signaling but also demonstrates a diverse range of biological functions. Despite the increasing focus on GPER, there remain many uncertainties regarding its specific localization within various organelles and the subsequent impact on its biological functions. This review discusses the research progress of GPER localization in the cell membrane, endoplasmic reticulum membrane, and potential mitochondrial localization. It explores the mechanisms by which GPER is involved in tumorigenesis and metastasis, metabolic regulation, cardiovascular protection, and neurological functions. Additionally, it analyzes how GPER’s intracellular localization influences its biological activities and proposes future research directions regarding the regulatory mechanisms of localization and its clinical application potential, aiming to provide new targets for clinical therapy.

CSTR: 32200.14.cjcb.2025.08.0035