NPPB (natriuretic peptide B) is a cardiac hormone that plays a critical role in cardio-renal homeostasis and blood pressure regulation 1. The gene encodes brain natriuretic peptide (BNP), a stress-responsive marker predominantly expressed in the heart during embryonic and fetal stages; upon cardiac stress, NPPB expression is strongly upregulated in ventricular myocardium alongside its paralog NPPA 2. Mechanistically, NPPB functions through the receptor guanylyl cyclase signaling pathway to promote cGMP production, exerting negative regulation of systemic arterial blood pressure and diuretic hormone activity 1. In disease contexts, NPPB upregulation serves as a hallmark of cardiac pathology: aberrant NPPB expression occurs through YAP1/TAZ activation in mesothelioma with Hippo pathway mutations 3, and NPPB levels correlate with cardiomyopathy severity in TNNT2-variant-associated disease 4. Transcriptional dysregulation of NPPB through altered chr1 topology and transcription factor activity characterizes dilated cardiomyopathy pathogenesis 5, while cardiac hypertrophy involves NEU1-GATA4 and USP13-STAT1 signaling axes controlling NPPB transcription 67. Clinically, circulating NT-proBNP (NPPB's N-terminal fragment) serves as a sensitive biomarker for cardiac dysfunction diagnosis and prognostication, with genetic variants in the NPPB locus influencing circulating levels 8.