Zincology: Decoding Homeostasis to Unveil Disease Mechanisms

Zincology, the rigorous cross-disciplinary study of zinc metabolism and its multifaceted biological and applied roles in health and disease, delivers a transformative framework for resolving long-standing uncertainties in biomedical research. As a central regulator of cellular function and a versatile element in applied fields, zinc dyshomeostasis underpins diverse high-burden pathologies, including renal, metabolic, cardiovascular, and neurodegenerative disorders, yet its mechanisms remain fragmented across disciplines. This Perspective marks the first formal definition of Zincology as a distinct cross-disciplinary discipline, clarifying zinc's context-dependent dual role: systemic deficiency exacerbates biological injury through compromised antioxidant defense and inflammation, while local excess drives pathogenesis-exemplified by the Zn-protein kinase B (AKT)-forkhead box protein O1 (FOXO1)-glucose-6-phosphatase catalytic subunit (G6PC) axis in kidney disease. We synthesize Zincology's core principles to integrate systemic and local zinc metabolism, dissect its pathogenic role in the aforementioned disorders, and outline cross-disciplinary research directions with implications extending beyond biomedicine. Leveraging Zincology's multidisciplinary rigor, we establish zinc homeostasis as a unifying framework for deciphering disease mechanisms, with kidney disease serving as a paradigmatic model to validate its core tenets, bridging fragmented basic, clinical, industrial, and environmental research to address global critical unmet medical and societal needs. Notably, Zincology extends beyond biomedicine to encompass engineering, ecology, and other frontier fields, representing a comprehensive cross-disciplinary system that links basic science with diverse applied domains.