A membrane protein insertion complex Membrane proteins make up one-quarter of the human proteome and are required for all aspects of cell-to-cell communication, signaling, and transport. Defects in membrane protein biogenesis underlie a variety of human diseases, and half of all therapeutic drugs target an integral membrane protein. Pleiner et al. describe the cryo–electron microscopy structure of the human endoplasmic reticulum (ER) membrane protein complex, a large oligomeric assembly involved in the biogenesis of membrane proteins in the ER. This structure helps to explain how this complex captures and then inserts nascent proteins into the lipid bilayer, elucidating the molecular details of a fundamental biological process with broad biomedical implications. Science , this issue p. 433