biostudies-literatureKukulage DSKNHLBI NIH HHSNational Institutes of HealthNational Heart Lung and Blood InstituteNational Institute of General Medical SciencesNIGMS NIH HHS102221https://www.ebi.ac.uk/biostudies/studies/S-EPMC9844265biostudies-literatureUnknown71Protein S-glutathionylation serves a regulatory role in proteins and modulates distinct biological processes implicated in health and diseases. Despite challenges in analyzing the dynamic and reversible nature of S-glutathionylation, recent chemical and biological methods have significantly advanced the field of S-glutathionylation, culminating in selective identification and detection, structural motif analysis, and functional studies of S-glutathionylation. This review will highlight emerging studies of protein glutathionylation, beginning by introducing biochemical tools that enable mass spectrometric identification and live-cell imaging of S-glutathionylation. Next, it will spotlight recent examples of S-glutathionylation regulating physiology and inflammation. Lastly, we will feature two emerging lines of glutathionylation research in cryptic cysteine glutathionylation and protein C-glutathionylation.Current opinion in chemical biologyEmerging chemistry and biology in protein glutathionylation.PMC9844265R01 GM143214R01 HL131740Kukulage DSKMatarage Don NNJAhn YHfalseEmerging chemistry and biology in protein glutathionylation.Protein S-glutathionylation serves a regulatory role in proteins and modulates distinct biological processes implicated in health and diseases. Despite challenges in analyzing the dynamic and reversible nature of S-glutathionylation, recent chemical and biological methods have significantly advanced the field of S-glutathionylation, culminating in selective identification and detection, structural motif analysis, and functional studies of S-glutathionylation. This review will highlight emerging studies of protein glutathionylation, beginning by introducing biochemical tools that enable mass spectrometric identification and live-cell imaging of S-glutathionylation. Next, it will spotlight recent examples of S-glutathionylation regulating physiology and inflammation. Lastly, we will feature two emerging lines of glutathionylation research in cryptic cysteine glutathionylation and protein C-glutathionylation.2022-01-01T00:00:00Z2022 Dec2025-05-29T21:47:19.495Z2025-05-29T21:47:19.495ZS-EPMC98442653622370010.1016/j.cbpa.2022.102221