Despite advances in pharmacologic and procedural therapies, heart failure (HF) and cardiac arrhythmias remain significant global health burdens, highlighting the urgent need for novel therapeutic strategies. Defective Ca 2+ handling in cardiac myocytes is recognized as a central pathogenic mechanism underlying both heart failure and atrial and ventricular arrhythmias. In this review, we critically assess the current state of research on Ca 2+ -handling proteins and their role in causing heart failure and arrhythmias, highlighting therapeutic implications. Recent paradigm-shifting discoveries, clinical trial outcomes, and challenges of targeting Ca 2+ -handling proteins are examined. As outlined in this review, an improved understanding of the relevant proteins and their differential expression and function in human health and disease is crucial for developing Ca 2+ handling–targeted therapeutics that can fundamentally alter the natural history of heart failure and arrhythmias.
Redel‐Traub et al. (2025) studied this question.