GPER1 is a G protein-coupled membrane estrogen receptor that binds 17β-estradiol with high affinity, mediating rapid non-genomic signaling 1. Upon activation, GPER1 stimulates multiple intracellular pathways including cAMP production, calcium mobilization, and Src-mediated EGFR transactivation through HB-EGF release, activating downstream PI3K/Akt and ERK/MAPK cascades 2. GPER1 also functions as an aldosterone receptor regulating vascular contractility. Physiologically, GPER1 mediates cardioprotection, blood pressure regulation through vasodilation, glucose homeostasis via pancreatic beta-cell insulin secretion, neuroprotection in hippocampal neurons, and immune regulation by attenuating TNF-mediated leukocyte adhesion 2. In cancer contexts, GPER1 shows complex roles: it suppresses ferroptosis in lung cancer via PI3K/AKT/mTOR-SREBP1/SCD1 signaling, promoting cisplatin resistance 3, while inducing centrosome amplification and chr7 instability in colon cancer 4. Additionally, GPER1 activation restricts macrophage proliferation in hepatocellular carcinoma through MEK/ERK pathway downregulation, correlating with improved patient survival 5. GPER1 dysregulation associates with multiple diseases including reproductive disorders, breast/ovarian/lung cancers, cardiovascular disease, and metabolic disorders 6. Its distinct non-genomic mechanism and tissue-specific effects differentiate GPER1 from nuclear estrogen receptors, offering potential therapeutic opportunities.