The cellular activities of ribosomes, the molecular machines that synthesize proteins, regulate gene expression during many physiological processes such as blood cell differentiation. A collaboration between the Shao Lab and the Brown Lab (HMS BCMP) has identified new silencing interactions on ribosomes. Their paper in eLife computationally mined single-particle electron cryo-microscopy (cryo-EM) data of ribosomes to determine structures of inactive ribosomes containing a new tRNA binding site and protein, IFRD2. IFRD2 binds to the catalytic core of ribosomes to preclude protein synthesis. These findings provide molecular insights into how ribosomal interactions may inactivate translation to regulate gene expression.