Abstract
Repeat sequences account for approximately 45% of the human genome, and can produce noncanonical DNA secondary structures that include G-quadruplexes (G4s). Among these, G4s are unique, in that their formation and stability are largely influenced by metal cations, such as Na(＋), K(＋), Ca(2＋), and Mg(2＋). These cations stabilize G4 structures, while also influencing their folding and biological activities. Interactions between G4s and metal ions affect key cellular processes that include transcription, replication, and genome stability. This review highlights the structural diversity and functional roles of G4s, and further explores how their ion-dependent properties have been harnessed for applications in biosensing and therapeutic development. Future research directions to advance G4-targeted technologies for both diagnostic and clinical use are also discussed. [BMB Reports 2025; 58(9): 397-405].