Recent studies have revealed that genomes contain thousands of small open reading frames that encode microproteins, but the functional significance of microproteins is unclear. D'Lima et al. now report the identification of a human microprotein, NoBody (non-annotated P-body dissociating polypeptide), that interacts with the mRNA decapping complex. Functional proteomics studies showed that NoBody interacts with the decapping complex, which removes the 5′cap from mRNAs to promote decay, by directly binding to enhancer of decapping protein 4. At low expression levels, NoBody localized to cytoplasmic P-bodies (RNA−protein granules that are involved in mRNA decay). NoBody overexpression induced the dispersal of P-bodies, whereas silencing its expression increased the number of P-bodies. Moreover, NoBody overexpression increased the levels of a nonsense-mediated decay substrate, which suggests that NoBody inhibits mRNA decay, although the exact mechanisms remain to be elucidated.