An overview of the chemical basis for triggering the S-glutathionylation of proteins, including cMyBP-C. S-glutathionylation is the forming a disulfide bond between a target protein and GSSG (PSSG). This reaction often occurs when the ratio of GSH/GSSG is lowered, secondary to increased ROS. The reaction can occur spontaneously with GSSG as a substrate or can be enzymatically catalyzed by GSH S-transferase (GST). The S-glutathionylation of proteins is an alternative pathway from the forming of sulfonic acid, which is also triggered during oxidative stress and leads to proteolysis. The reversal, or deglutathionylation of proteins, can occur spontaneously with the thiol-disulfide exchange of GSH or enzymatically with the help of Grx. Figure made using BioRender.