The cardiac ryanodine receptor (RyR2) is an intracellular Ca²⁺ release channel vital for the function of the heart. Physiologically, RyR2 is triggered to release Ca²⁺ from the sarcoplasmic reticulum (SR) which enables cardiac contraction; however, spontaneous Ca²⁺ leak from RyR2 has been implicated in the pathophysiology of heart failure (HF). RyR2 channels have been well documented to assemble into clusters within the SR membrane, with the organisation of RyR2 clusters recently gaining interest as a mechanism by which the occurrence of pathological Ca²⁺ leak is regulated, including in HF. In this review, we explain the terminology relating to key nanoscale RyR2 clustering properties as both single clusters and functionally grouped Ca²⁺ release units, with a focus on the advancements in super-resolution imaging approaches which have enabled the detailed study of cluster organisation. Further, we discuss proposed mechanisms for modulating RyR2 channel organisation and the debate regarding the potential impact of cluster organisation on Ca²⁺ leak activity. Finally, recent experimental evidence investigating the nanoscale remodelling and functional alterations of RyR2 clusters in HF is discussed with consideration of the clinical implications.

心脏兰尼碱受体 (RyR2) 是一种细胞内 Ca ²⁺释放通道，对心脏功能至关重要。生理上，RyR2 被触发从肌浆网 (SR)释放 Ca ^{2+ ，从而使心脏收缩；}然而，RyR2 的自发 Ca ²⁺渗漏与心力衰竭 (HF) 的病理生理学有关。RyR2 通道已被充分证明可在 SR 膜内组装成簇，RyR2 簇的组织最近作为调节病理性 Ca ²⁺泄漏（包括在 HF 中）发生的机制而引起人们的兴趣。在这篇综述中，我们将与关键纳米级 RyR2 聚类特性相关的术语解释为单个簇和功能分组的 Ca ²⁺释放单元，重点关注超分辨率成像方法的进步，这些方法使得能够对簇组织进行详细研究。^{此外，我们讨论了调节 RyR2 通道组织的拟议机制以及有关簇组织对 Ca 2+}泄漏活动的潜在影响的争论。最后，讨论了最近研究 HF 中 RyR2 簇的纳米级重塑和功能改变的实验证据，并考虑了临床意义。