The chapter "Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery" by Candice E. Paulsen and Kate S. Carroll from the Department of Chemistry at The Scripps Research Institute provides an in-depth overview of the role of cysteine residues in redox signaling. The authors discuss the reactivity and oxidant sensitivity of cysteine residues, methods to identify low-pKₐ cysteine residues, and the production and metabolism of reactive oxygen species (ROS) in biological systems. They also explore the modification of protein cysteine thiols by ROS, including methods for detecting these modifications. Additionally, the chapter covers reactive nitrogen species (RNS) and their role in biological systems, as well as the modification of protein cysteine thiols by RNS. The section on reactive sulfur species (RSS) discusses the production and metabolism of hydrogen sulfide (H₂S) and its modification of protein cysteine thiols. The authors conclude with a discussion on the future perspectives and ongoing efforts to elucidate the role of cysteine oxPTMs in health and disease. The chapter emphasizes the importance of cysteine residues as sensors and targets of reactive intermediates in cellular signaling pathways and highlights the challenges and recent advancements in detecting these modifications.The chapter "Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery" by Candice E. Paulsen and Kate S. Carroll from the Department of Chemistry at The Scripps Research Institute provides an in-depth overview of the role of cysteine residues in redox signaling. The authors discuss the reactivity and oxidant sensitivity of cysteine residues, methods to identify low-pKₐ cysteine residues, and the production and metabolism of reactive oxygen species (ROS) in biological systems. They also explore the modification of protein cysteine thiols by ROS, including methods for detecting these modifications. Additionally, the chapter covers reactive nitrogen species (RNS) and their role in biological systems, as well as the modification of protein cysteine thiols by RNS. The section on reactive sulfur species (RSS) discusses the production and metabolism of hydrogen sulfide (H₂S) and its modification of protein cysteine thiols. The authors conclude with a discussion on the future perspectives and ongoing efforts to elucidate the role of cysteine oxPTMs in health and disease. The chapter emphasizes the importance of cysteine residues as sensors and targets of reactive intermediates in cellular signaling pathways and highlights the challenges and recent advancements in detecting these modifications.