The precision of cellular processes is intrinsically limited, which implies that cells naturally make mistakes. In addition, cells are exposed to a multitude of stresses, both internal and environmental, which can induce molecular damage. This can occur at many levels: at the DNA level, for example as a result of DNA replication errors or exposure to mutagenizing agents; at the RNA level, from errors that arise during transcription or post-transcriptional processing; and at the protein level, owing to defects in protein-folding pathways.

To minimize or prevent the accumulation of such damage, cells have developed cytoprotective quality control systems. These prevent errors from occurring, by safeguarding the molecular systems that orchestrate these processes. If damage has occurred, they detect damaged or abnormal macromolecules and initiate either their repair or their degradation. In addition, quality control systems can trigger more 'global' stress responses that increase a cell's capacity to cope with stress when local responses are not sufficient. Notably, a failure to carry out these cytoprotective responses has been linked to ageing and disease, including neurodegeneration caused by the accumulation of misfolded protein aggregates.

This specially commissioned Focus issue highlights key examples of quality control systems that are in place at the RNA and protein levels and in which our structural and molecular understanding is advancing.