Abstract
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.