Recent findings point to a novel translational quality control pathway for secretory proteins that pre-empts mutant protein production and aggregation by inducing mRNA degradation. Karamyshev et al. found that the pathway is triggered if signal sequences within the nascent chain fail to interact correctly with the signal recognition particle (SRP) when exiting the ribosome, which shifts the proximity of the nascent chain from the SRP to the protein argonaute2 (AGO2). Knockdown or overexpression of AGO2 prevented or induced degradation of mRNA containing mutated signal sequences, respectively. Finally, knockdown of SRP54 was shown to also promote the degradation of secretory protein mRNA.