Phospholamban R14del disease: The past, the present and the future

作者：Elizabeth Vafiadaki, Pieter C. Glijnis, Pieter A. Doevendans, Evangelia G. Kranias, Despina Sanoudou · 发表于：Frontiers in Cardiovascular Medicine · 年份：2023 · DOI：10.3389/fcvm.2023.1162205 · 被引用次数：26 · 研究领域：Genomics and Rare Diseases、Genetics and Neurodevelopmental Disorders、Mitochondrial Function and Pathology

Arrhythmogenic cardiomyopathy affects significant number of patients worldwide and is characterized by life-threatening ventricular arrhythmias and sudden cardiac death. Mutations in multiple genes with diverse functions have been reported to date including phospholamban (PLN), a key regulator of sarcoplasmic reticulum (SR) Ca 2+ homeostasis and cardiac contractility. The PLN-R14del variant in specific is recognized as the cause in an increasing number of patients worldwide, and extensive investigations have enabled rapid advances towards the delineation of PLN-R14del disease pathogenesis and discovery of an effective treatment. We provide a critical overview of current knowledge on PLN-R14del disease pathophysiology, including clinical, animal model, cellular and biochemical studies, as well as diverse therapeutic approaches that are being pursued. The milestones achieved in <20 years, since the discovery of the PLN R14del mutation (2006), serve as a paradigm of international scientific collaboration and patient involvement towards finding a cure.