Small signaling peptides are important mediators of intercellular communication in multicellular systems, including plants. Despite their importance, most plant peptide encoding genes remain uncharacterized, mostly due to their small open reading frames, and only a limited number of loss-of-function mutants have up until now been available for study. To circumvent this caveat, Yamaguchi et al. (pp. 1848-1856) have designed a series of gene targeting vectors for CLE-peptide-encoding genes and generated mutants. This mutant collection will provide opportunities to functionally characterize peptide-encoding genes and illustrate the usefulness of CRISPR/Cas9 for investigating cell signaling.