Bruno Reversade and colleagues identify a highly conserved gene encoding a peptide hormone required for cardiac development in zebrafish (Dev. Cell doi:10.1016/j.devcel.2013.11.002, 5 December 2013). The gene, ELABELA, is found on human chromosome 4 and was previously identified as a noncoding RNA. However, the authors found that ELA contains a conserved ORF predicted to express a 54-residue secreted protein. The mature form of ELA is only 32 amino acids, with the last 13 residues being nearly invariant among all sequenced vertebrates. The authors used an allelic series of zebrafish ela mutants to show that Ela deficiency leads to severe defects in cardiac morphogenesis and often results in the complete absence of a heart. The ela mutant phenotype is similar to that of Apelin receptor (Aplnr) mutants, and both Ela and Aplnr are expressed before gastrulation. In contrast, the mutant for the currently accepted Aplnr ligand, Apelin, does not recapitulate the Aplnr phenotype, and Apelin is expressed only later in development. These results indicate that ELABELA is the Aplnr ligand responsible for cardiac development. ELA is expressed in human embryonic stem cells and adult human prostate and kidney. The authors suggest that ELA may have cardioprotective and/or vasodilatory properties in humans, as does Apelin.