The role of zinc transporter 1 (ZnT1) in health and disease: From molecular mechanisms to therapeutic opportunities.

Zinc transporter 1 (ZnT1/SLC30A1) is a major plasma membrane-localized zinc efflux transporter and acts as a central regulator of cellular metal homeostasis. Beyond exporting Zn2+, recent evidence reveals that ZnT1 also transports Cu2+ and serves as a molecular hub linking zinc-copper interplay, redox balance, immune signaling and programmed cell death. This review summarizes current advances in ZnT1 structure, transport mechanism, regulatory networks and physiological roles across the gut-liver-immune-neuro-cardiovascular axis. We further outline its pathological involvement in Wilson disease, amyotrophic lateral sclerosis, cancer and inflammatory disorders, highlighting ferroptosis, cuproptosis and metabolic reprogramming as key downstream consequences of ZnT1 dysregulation. Emerging therapeutic approaches include small-molecule modulators, RNA-based regulation, antibody targeting and metal-based interventions. Although challenges remain-such as tissue specificity, systemic toxicity and biomarker development-ZnT1 is rapidly evolving from a basic transport protein to a promising precision medicine target. Continued efforts in structural biology, single-cell metallomics and targeted delivery systems will accelerate its clinical translation.