Beyond Natriuretic Peptides: Corin and Furin As Phenotype-Specific Biomarkers and Therapeutic Gatekeepers in Heart...

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, with a growing need for improved understanding of disease mechanisms and better strategies for risk stratification. Among the key systems involved in maintaining cardiovascular homeostasis is the natriuretic peptide pathway, which is dependent on two critical enzymes: Corin, a cardiac-restricted serine protease, and Furin, a ubiquitous convertase. These enzymes activate pro-atrial and pro-brain natriuretic peptides that facilitate natriuresis, vasodilation, and neurohormonal balance. Disruption of the corin-furin axis impairs peptide activation and contributes to the maladaptive processes that lead to the progression of heart failure (HF). While several studies have reported altered expression of corin and furin in different HF phenotypes, their value as clinical biomarkers remains limited. Current diagnostic performance shows only modest sensitivity and specificity compared to established markers such as BNP and NT-proBNP, and incremental benefit has yet to be demonstrated in clinical settings. Nonetheless, their ability to reflect upstream enzymatic processes offers important mechanistic insight into HF pathophysiology. Looking ahead, corin and furin may hold promise as adjunctive or mechanistic biomarkers to guide therapies targeting natriuretic peptide-related pathways. This review provides a critical overview of the physiological and pathological roles of corin and furin in heart failure and evaluates current evidence for their potential as biomarkers. It also discusses key limitations and highlights future directions for research and therapeutic translation.