Sheard et al. (2022) used enhanced expansion microscopy to demonstrate that RyR2 clusters in failing myocytes frequently exhibit a frayed appearance, where small groups of channels detach from the main cluster, particularly in regions depleted of the structural protein junctophilin-2. Similarly, Kolstad et al. (2018) showed that post-infarction heart failure is characterized by RyR2 cluster dispersion and fragmentation, resulting in smaller, more numerous cluster fragments with reduced inter-channel connectivity. This evidence concerns the gene JPH2 and heart failure.