The molecular, metabolic, and clinical aspects of human selenoproteins: a narrative review of the last ten years

Abstract

Selenium (Se) is an essential trace element required for numerous physiological processes, including antioxidant defense, redox homeostasis, immune regulation, thyroid hormone metabolism, and endoplasmic reticulum function. The biological activities of Se are primarily mediated through its incorporation into selenoproteins as selenocysteine (Sec), the 21st proteinogenic amino acid. Over the past decade, substantial advances have expanded our understanding of the molecular, metabolic, and clinical significance of human selenoproteins in health and disease. This narrative review aims to comprehensively summarize recent advances in the molecular biology, metabolism, physiological functions, and clinical relevance of human selenoproteins published during the last ten years. Particular emphasis is placed on their roles in human diseases, emerging therapeutic applications, and future research directions. A comprehensive narrative literature review was conducted by examining peer-reviewed studies published over the past decade using major scientific databases, including PubMed, Scopus, and Web of Science. Relevant original research articles, clinical studies, and review papers addressing selenium metabolism, selenoprotein biology, molecular mechanisms, and clinical implications were critically evaluated and synthesized. Recent evidence demonstrates that human selenoproteins regulate diverse biological processes, including antioxidant defense, maintenance of cellular redox balance, thyroid hormone activation, calcium signaling, protein folding, endoplasmic reticulum homeostasis, immune regulation, inflammation, and cellular metabolism. Dysregulation of selenoprotein expression or function has been associated with numerous pathological conditions, including cardiovascular diseases, metabolic disorders, neurodegenerative diseases, cancer, reproductive dysfunction, thyroid disorders, and inflammatory diseases. Advances in molecular biology have further revealed tissue-specific functions of individual selenoproteins and highlighted their potential as diagnostic biomarkers and therapeutic targets. However, the narrow therapeutic window between selenium deficiency and toxicity underscores the importance of maintaining optimal selenium homeostasis. Human selenoproteins play indispensable roles in maintaining physiological homeostasis and protecting against a broad spectrum of diseases. Continued investigation of selenium metabolism, selenoprotein regulation, and their interactions with cellular signaling pathways will improve understanding of disease pathogenesis and facilitate the development of precision selenium-based therapeutic strategies. Future research should focus on elucidating the functions of less-characterized selenoproteins, identifying reliable biomarkers of selenium status, and conducting well-designed clinical trials to establish safe and effective selenium supplementation protocols for disease prevention and treatment.