Overview of the Zinc Functional Interactome Through Health Hallmarks and Medical Conditions

Zinc is an essential micronutrient involved in structural, catalytic, and regulatory functions across all levels of biological organization. Despite substantial advances over the past two decades, the zinc literature remains highly fragmented, with mechanistic, nutritional, and clinical findings often reported in isolation. Additionally, the synergistic interactions between zinc and other micronutrients-particularly minerals and vitamins-are dispersed across multiple research domains, complicating efforts to understand their integrated roles in maintaining homeostasis. Recent developments in artificial intelligence (AI) present new opportunities to consolidate these data, enabling multi-scale analyses of zinc-dependent processes and the broader zinc interactome. Although a complete map of the zinc interactome is not yet feasible, an integrative perspective is needed to contextualize zinc's contributions within the framework of the hallmarks of health. This narrative review highlights zinc's involvement in cellular maintenance, metabolic regulation, stress response, and systemic physiological function. It further examines how disruptions in zinc status, alone or in combination with other nutrient imbalances, contribute to clinically relevant disorders. By combining current knowledge across molecular, cellular, and systems biology levels, this review illustrates zinc's pleiotropic effects on physiological resilience and healthspan, with particular emphasis on its role in nutritional status, homeostatic regulation, and overall human health.