Differences between translation termination at a physiological stop codon (upper panel) and at a premature termination codon (lower panel). When translation stops at a physiological stop codon, the PABPC1 protein recruits eRF1 and helps position it in the A site of the ribosome. When the ribosome pauses on a PTC, PABPC1 is too far away and it’s the UPF3X protein which helps eRF1 to recognize the stop codon, albeit more slowly. This slowdown promotes activation of NMD.