GPR30

GPR30, also known as GPER1, is a G protein-coupled receptor that functions as a membrane-bound estrogen receptor, mediating rapid, non-genomic signaling distinct from the classical nuclear estrogen receptors ERα and ERβ. First identified as a potential estrogen receptor in the early 2000s and later characterized as a G protein-coupled receptor, GPER is encoded by the GPER1 gene.

Upon binding estrogens such as 17β-estradiol, GPER activates intracellular signaling pathways including the Gs-adenylyl cyclase-cAMP axis, calcium mobilization, and activation of mitogen-activated protein kinase (MAPK/ERK) and PI3K/Akt cascades. It can also promote transactivation of receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR). GPER is found at the plasma membrane and in intracellular compartments like the endoplasmic reticulum, contributing to rapid cellular responses to estrogen.

Physiologically, GPER has been implicated in diverse processes including vascular function, metabolism, reproductive tissue signaling, and cancer biology. In breast cancer, GPER signaling may influence tumor cell proliferation and migration, though its precise role is context-dependent and the extent of its contribution to estrogen actions remains a topic of ongoing research and some debate within the field. Researchers continue to explore its potential as a therapeutic target.