Gammons et al. (Gammons et al., 2021) showed that both constitutive and inducible cardiomyocyte-specific deletion of Orai3 develop a phenotype consistent with dilated cardiomyopathy, with increased fibrosis, increased mortality, ultrastructural changes in mitochondria, increased mitochondrial fission, and abnormal sarcomeric structure; highlighting a potentially important regulatory role of Orai3 in the heart. Here, ORAI3 is linked to dilated cardiomyopathy.