biostudies-literatureBeck DBNIAMS NIH HHS435-447https://www.ebi.ac.uk/biostudies/studies/S-EPMC9075716biostudies-literatureUnknown18(8)Ubiquitylation is an essential post-translational modification that regulates intracellular signalling networks by triggering proteasomal substrate degradation, changing the activity of substrates or mediating changes in proteins that interact with substrates. Hundreds of enzymes participate in reversible ubiquitylation of proteins, some acting globally and others targeting specific proteins. Ubiquitylation is essential for innate immune responses, as it facilitates rapid regulation of inflammatory pathways, thereby ensuring sufficient but not excessive responses. A growing number of inborn errors of immunity are attributed to dysregulated ubiquitylation. These genetic disorders exhibit broad clinical manifestations, ranging from susceptibility to infection to autoinflammatory and/or autoiNature reviews. RheumatologyDisorders of ubiquitylation: unchained inflammation.PMC9075716R00 AR078205Kastner DLWerner ABeck DBAksentijevich IfalseDisorders of ubiquitylation: unchained inflammation.Ubiquitylation is an essential post-translational modification that regulates intracellular signalling networks by triggering proteasomal substrate degradation, changing the activity of substrates or mediating changes in proteins that interact with substrates. Hundreds of enzymes participate in reversible ubiquitylation of proteins, some acting globally and others targeting specific proteins. Ubiquitylation is essential for innate immune responses, as it facilitates rapid regulation of inflammatory pathways, thereby ensuring sufficient but not excessive responses. A growing number of inborn errors of immunity are attributed to dysregulated ubiquitylation. These genetic disorders exhibit broad clinical manifestations, ranging from susceptibility to infection to autoinflammatory and/or autoi2022-01-01T00:00:00Z2022 Aug2025-04-04T08:01:38.81Z2024-11-19T22:23:49.06ZS-EPMC90757163552396310.1038/s41584-022-00778-4