Integral membrane proteins are synthesized in the endoplasmic reticulum (ER), where they are co-translationally incorporated into the membrane. This depends on hydrophobic sequences, which stop further transfer into the ER lumen. However, many multipass transmembrane proteins have regions of low hydrophobicity. Here, the authors use αβ T cell receptor (αβTCR; which crosses the secretory pathway only when correctly assembled) as a model to determine the quality control mechanisms underlying this process. They found that unassembled α-chains, which have a transmembrane domain of low hydrophobicity, enter the ER lumen fully. Here, this domain is recognized by BiP (binding immunoglobulin protein), a chaperone of the ER quality control machinery, which initiates α-chain degradation. However, association with the CD3 co-receptor subunits CD3δ and CD3ɛ allows integration of the α-chains into the ER membrane and stabilizes them for subsequent assembly into the complete αβTCR–CD3 complex.