2023-07-142023-07-142023Karamysheva, Z.N., & Karamyshev, A.L.. 2023. Aberrant protein targeting activates quality control on the ribosome. Frontiers in Cell and Developmental Biology, 11. https://doi.org/10.3389/fcell.2023.1198184https://doi.org/10.3389/fcell.2023.1198184https://hdl.handle.net/2346/94936cc-byCells synthesize thousands of different proteins that should be delivered to different cellular compartments, integrated into membranes, or secreted outside of the cell to conduct their functions. Over 20 thousand genes are detected in a human genome including about 3,000 genes encoding secreted proteins and 5,500 genes encoding membrane proteins (Uhlen et al., 2015). Thus, about 40% of all proteins are transported through or integrated into cellular membranes. What happens to secretory/membrane proteins that are not able to be targeted to the endoplasmic reticulum (ER) because of the mutations in the signal peptides or defects in the protein transport machinery? These proteins are potentially harmful to cells if they are mislocalized. In this article we discuss secretory protein targeting, signal peptides interactions with transport machinery of the cells, defects in these processes, their possible implications in human diseases, and cellular mechanisms preventing synthesis of defective secretory proteins.engdiseaseprotein quality controlprotein sortingprotein targeting and transportribosomeRNA degradationsignal peptidesignal recognition particle (SRP)Note