Zinc (Zn), which is an essential trace element, is involved in numerous mammalian physiological events; therefore, either a deficiency or excess of Zn impairs cellular machineries and influences physiological events, such as systemic growth, bone homeostasis, skin formation, immune responses, endocrine function, and neuronal function. Zn transporters are thought to mainly contribute to Zn homeostasis within cells and in the whole body. Recent genetic, cellular, and molecular studies of Zn transporters highlight the dynamic role of Zn as a signaling mediator linking several cellular events and signaling pathways. Dysfunction in Zn transporters causes various diseases. This review aims to provide an update of Zn transporters and Zn signaling studies and discusses the remaining questions and future directions by focusing on recent progress in determining the roles of SLC39A/ZIP family members in vivo.

Zinc is an essential trace element that plays an important physiological role in numerous cellular processes. Zinc deficiency can result in diverse symptoms, such as impairment of the immune response, skin disorders, and impairments in cardiovascular functions. Recent reports have demonstrated that zinc acts as a signaling molecule, and its signaling pathways, referred to as zinc signals, are related to the molecular mechanisms of cardiovascular functions. Therefore, comprehensive understanding of the significance of zinc-mediated signaling pathways is vital as a function of zinc as a nutritional component and of its molecular mechanisms and targets. Several basic and clinical studies have reported the relationship between zinc level and the onset and pathology of cardiovascular diseases, which has attracted much attention in recent years. In this review, we summarize the recent findings regarding the effects of zinc on cardiovascular function. We also discuss the importance of maintaining zinc homeostasis in the cardiovascular system and its therapeutic potential as a novel drug target.

The first manifestations that appear under zinc deficiency are skin defects such as dermatitis, alopecia, acne, eczema, dry, and scaling skin. Several genetic disorders including acrodermatitis enteropathica (also known as Danbolt-Closs syndrome) and Brandt’s syndrome are highly related to zinc deficiency. However, the zinc-related molecular mechanisms underlying normal skin development and homeostasis, as well as the mechanism by which disturbed zinc homeostasis causes such skin disorders, are unknown. Recent genomic approaches have revealed the physiological importance of zinc transporters in skin formation and clarified their functional impairment in cutaneous pathogenesis. In this review, we provide an overview of the relationships between zinc deficiency and skin disorders, focusing on the roles of zinc transporters in the skin. We also discuss therapeutic outlooks and advantages of controlling zinc levels via zinc transporters to prevent cutaneous disorganization.

Ion channels and transporter proteins are essential regulators of cellular homeostasis, and they are involved in virtually every aspect of physiology, including electrical signalling, ion and metabolite transport, and intracellular communication. Dysregulation of these membrane proteins contributes to the pathogenesis of numerous diseases, making them important therapeutic targets across diverse medical fields. Consequently, understanding the molecular mechanisms that govern their structure, function, and regulation remains a major focus of both basic and translational research.In recent years, remarkable advances in experimental and computational methodologies have transformed the study of ion channels and transporters. New The articles included in this collection highlight complementary perspectives spanning structural biology, computational approaches, disease mechanisms, pharmacological modulation, and emerging therapeutic strategies. Collectively, they illustrate how innovative methodologies continue to deepen our understanding of ion channel and transporter biology while opening new avenues for therapeutic intervention.The five review articles included here illustrate how recent advances in structural biology, the application of AI, disease-oriented ion channel research, and molecular trafficking studies are helping to reshape our understanding of ion channels and transporter proteins, providing new opportunities for therapeutic intervention. The three original articles complement these broader perspectives by providing new experimental evidence on channel gating, membrane trafficking, and pharmacological modulation. Together, these original studies demonstrate how complementary approaches that include experimental, structural, and pharmacological approaches can refine our understanding of ion channel and transporter structure and function, paving the way to develop new more potent and selective drugs able to modulate these key proteins.Our understanding of ion channels and transporters, including their structures, molecular mechanisms, and physiological regulation has advanced considerably over the past decades. Those intensive research efforts have contributed to the identification of disease mechanisms and the evaluation of ion channels and transporters as therapeutic targets, thereby strengthening the link between basic research and translational applications.However, major challenges remain. Ion channels and transporters are regulated by complex conformational dynamics, subcellular trafficking, and interactions with diverse molecular partners, making it difficult to fully capture their behaviour using conventional experimental approaches alone. Overcoming these limitations requires a methodological innovation that integrates structural biology, physiology, pharmacology, and computational approaches.As highlighted by several contributions in this Research Topic, AI-based methodologies are increasingly important in ion channel and transporter research. AI-assisted structural approaches offer powerful opportunities to analyse the dynamic conformational landscapes of channels and transporters, complementing experimental structural biology and expanding the scope of antibody-enabled structural investigations. AI-driven strategies may also accelerate the discovery and optimization of compounds that selectively modulate channel function, trafficking, or protein stability, strengthening the link between mechanistic studies and therapeutic development. In summary, the integration of experimental approaches with AI-based analyses will likely play a central role in overcoming many current technical limitations.This Research Topic illustrates how methodological innovation continues to advance the study of ion channels and transporter proteins from multiple perspectives. By bringing together contributions spanning a range of methodologies, this collection highlights both the breadth of the field and the expanding range of tools available to interrogate these important membrane proteins. Overcoming the challenge of translating fundamental mechanistic insights into clinical applications will require both continued experimental innovation and the effective integration of computational (especially AI-enabled) approaches.Given the remarkable diversity of ion channels and transporters, continued methodological innovation will be essential for advancing our understanding of their biology and therapeutic potential. Nevertheless, we hope that this Research Topic will provide interested readers with a useful and stimulating overview of the methodological advances, emerging concepts, and future directions shaping this evolving field.