NPR1 (natriuretic peptide receptor 1) is a membrane-bound guanylate cyclase receptor that functions as the primary effector for natriuretic peptides ANP and BNP 1. Upon ligand binding, NPR1 stimulates cGMP production, activating protein kinase cGMP-dependent 1 (PRKG1), which subsequently activates PRKAA1 to regulate vascular tone and blood pressure homeostasis 2. NPR1 plays an essential role in endothelial cell senescence regulation and vascular aging [UniProt Function]. In heart failure, NPR1 activation promotes vasodilation, diuresis, and natriuresis, lowering venous pressures and congestion 3. Genetic variants in NPR1 are associated with blood pressure changes and heart failure risk in large population studies 3. Beyond cardiovascular function, NPR1 promotes gastric cancer metastasis by activating lipid droplet lipolysis through PRKG1-mediated phosphorylation of hormone-sensitive lipase, enhancing mitochondrial oxidative phosphorylation and fueling cancer cell energy demands 2. Elevated NPR1 correlates with increased lymph node metastasis and shorter survival in gastric cancer patients 2. NPR1 agonists represent promising therapeutic targets for resistant hypertension and heart failure, with monoclonal agonist antibodies like REGN5381 demonstrating selective venous pressure reduction in clinical trials 13.