The role of ubiquitination in the pathogenesis of atrial fibrillation: mechanisms and therapeutic implications

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, defined by rapid and irregular atrial activation. Despite advances in AF treatment, AF remains a leading cause of cardiovascular morbidity and mortality worldwide. Emerging evidence demonstrates that ubiquitination, a dynamic post-translational modification, acts as a central regulator of AF pathogenesis by modulating inflammatory signaling, calcium dysregulation, ferroptosis, oxidative stress, and autophagy. This review systematically explores the multifaceted roles of ubiquitin-related enzymes (E3 ligases and deubiquitinating enzymes, DUBs) in AF pathogenesis, with an emphasis on their interactions with core molecular pathways. Furthermore, we discuss potential therapeutic strategies targeting the ubiquitin-proteasome system, and provide a framework for future translational research in AF.