Although some of the SUMO substrates that are modified during these diseases have been identified, for example, NaV1.5 for arrhythmia [32], PPARgamma for I/R [33] and PML for cardiac fibrosis [34], reports of SUMO modification of calcium handling proteins involved in excitation‐contraction coupling are restricted to the pioneering work of Hajjar and co‐workers on SERCA (reviewed in [22]). This evidence concerns the gene SCN5A and cardiac arrhythmia.