Abstract
O-linked-β-N-acetylglucosamine (O-GlcNAcylation) is a distinctive posttranslational protein modification involving the coordinated action of O-GlcNAc transferase and O-GlcNAcase, primarily targeting serine or threonine residues in various proteins. This modification impacts protein functionality, influencing stability, protein-protein interactions, and localization. Its interaction with other modifications such as phosphorylation and ubiquitination is becoming increasingly evident. Dysregulation of O-GlcNAcylation is associated with numerous human diseases, including diabetes, nervous system degeneration, and cancers. This review extensively explores the regulatory mechanisms of O-GlcNAcylation, its effects on cellular physiology, and its role in the pathogenesis of diseases. It examines the implications of aberrant O-GlcNAcylation in diabetes and tumorigenesis, highlighting novel insights into its potential role in cardiovascular diseases. The review also discusses the interplay of O-GlcNAcylation with other protein modifications and its impact on cell growth and metabolism. By synthesizing current research, this review elucidates the multifaceted roles of O-GlcNAcylation, providing a comprehensive reference for future studies. It underscores the potential of targeting the O-GlcNAcylation cycle in developing novel therapeutic strategies for various pathologies.