Cardiac contraction requires continuous cycles of calcium release and reuptake between the sarcoplasm and sarcoplasmic reticulum. In vertebrate cardiomyocytes, re-sequestration of calcium to the sarcoplasmic reticulum is accomplished by the SERCA whose activity is dampened by interaction with the small integral membrane proteins, phospholamban and sarcolipin. In a recent report published in Science, Magny et al identify 2 small peptides in Drosophila encoded in a putative long noncoding RNA that buffers calcium reuptake by sarco/endoplasmic reticulum Ca2+-ATPase 2a in a similar manner to sarco/endoplasmic reticulum Ca2+-ATPase 2a regulation by phospholamban and sarcolipin. These findings demonstrate that regulation of Ca2+-ATPases by small transmembrane peptides is a conserved and ancient strategy. Furthermore, this study highlights the possibility that there may be many undiscovered small peptides encoded within putative long non-coding RNAs that regulate important biological pathways.