NPR3 (natriuretic peptide receptor 3) is a multifunctional receptor that binds natriuretic peptides (ANP, BNP, and CNP) with similar affinities and functions primarily as a clearance receptor, regulating local concentrations of these peptide hormones 1. Beyond cardiovascular regulation, NPR3 exhibits dual receptor functionality: operating as a clearance receptor to modulate cGMP production through Npr1 activation, and as a signaling receptor controlling cAMP levels via adenylyl cyclase inhibition 1. This dual mechanism is essential for early embryonic development, particularly in neural crest and cranial placode progenitor formation 1. Genetically, NPR3 variants are associated with hypertensive disorders of pregnancy and blood pressure regulation 234. Population-specific studies confirm NPR3 polymorphisms correlate with hypertension in East Asian populations, though with ethnic heterogeneity 5. NPR3 also contributes to cardiac age acceleration, with genome-wide association studies identifying NPR3 loci linked to unfavorable cardiac geometry and systolic/diastolic dysfunction 6. Recently, NPR3 has been identified as a putative autoantigen in membranous nephropathy and membranous lupus nephritis, suggesting immune-mediated disease relevance 7. Additionally, NPR3 expression in gastric cancer endothelial cells facilitates tumor cell proliferation, indicating roles in cancer biology 8.