This review article by Zhang et al. provides a comprehensive overview of the role of reactive oxygen species (ROS) in cellular signaling pathways. ROS, which are generated through various intracellular and extracellular processes, have been recognized for their impact on cell fate, growth, differentiation, and death. The authors focus on the generation and homeostasis of intracellular ROS, as well as their interactions with key signaling proteins and pathways. Key points include: 1. **Homeostasis of ROS**: ROS levels are maintained in a dynamic equilibrium by both ROS-producing and ROS-eliminating processes. Mitochondrial oxidative metabolism and responses to xenobiotics are major sources of ROS. 2. **ROS and NF-κB Signaling Pathway**: ROS influence NF-κB activation by affecting IκBα phosphorylation and ubiquitination, and by modulating upstream kinases like MEKK1. 3. **ROS and MAPKs Signaling Pathway**: ROS activate various MAPKs (ERK, JNK, p38, BMK1) by oxidizing specific residues in their regulatory subunits, leading to downstream signaling. 4. **ROS and Keap1-Nrf2-ARE Signaling Pathway**: ROS dissociate Keap1 from Nrf2, promoting the activation of antioxidant genes and protecting against oxidative stress. 5. **ROS and PI3K-Akt Signaling Pathway**: ROS activate PI3K and inactivate PTEN, enhancing Akt activation and downstream signaling. 6. **Cross Talk between ROS and Ca²⁺**: Ca²⁺ modulates ROS generation and clearance, influencing cellular processes such as contraction and gene expression. 7. **ROS and mPTP**: ROS influence the opening of the mitochondrial permeability transition pore (mPTP), leading to mitochondrial dysfunction and apoptosis. 8. **ROS and Protein Kinase**: ROS oxidize cysteine residues in protein kinases, affecting their activity and downstream signaling. 9. **ROS and Ubiquitination/Proteasome System**: ROS can modify components of the ubiquitination/ Proteasome System, affecting protein degradation and cellular redox status. The authors conclude that understanding the mechanisms by which ROS regulate redox-associated signaling pathways is crucial for developing therapeutic strategies to address various pathologies.This review article by Zhang et al. provides a comprehensive overview of the role of reactive oxygen species (ROS) in cellular signaling pathways. ROS, which are generated through various intracellular and extracellular processes, have been recognized for their impact on cell fate, growth, differentiation, and death. The authors focus on the generation and homeostasis of intracellular ROS, as well as their interactions with key signaling proteins and pathways. Key points include: 1. **Homeostasis of ROS**: ROS levels are maintained in a dynamic equilibrium by both ROS-producing and ROS-eliminating processes. Mitochondrial oxidative metabolism and responses to xenobiotics are major sources of ROS. 2. **ROS and NF-κB Signaling Pathway**: ROS influence NF-κB activation by affecting IκBα phosphorylation and ubiquitination, and by modulating upstream kinases like MEKK1. 3. **ROS and MAPKs Signaling Pathway**: ROS activate various MAPKs (ERK, JNK, p38, BMK1) by oxidizing specific residues in their regulatory subunits, leading to downstream signaling. 4. **ROS and Keap1-Nrf2-ARE Signaling Pathway**: ROS dissociate Keap1 from Nrf2, promoting the activation of antioxidant genes and protecting against oxidative stress. 5. **ROS and PI3K-Akt Signaling Pathway**: ROS activate PI3K and inactivate PTEN, enhancing Akt activation and downstream signaling. 6. **Cross Talk between ROS and Ca²⁺**: Ca²⁺ modulates ROS generation and clearance, influencing cellular processes such as contraction and gene expression. 7. **ROS and mPTP**: ROS influence the opening of the mitochondrial permeability transition pore (mPTP), leading to mitochondrial dysfunction and apoptosis. 8. **ROS and Protein Kinase**: ROS oxidize cysteine residues in protein kinases, affecting their activity and downstream signaling. 9. **ROS and Ubiquitination/Proteasome System**: ROS can modify components of the ubiquitination/ Proteasome System, affecting protein degradation and cellular redox status. The authors conclude that understanding the mechanisms by which ROS regulate redox-associated signaling pathways is crucial for developing therapeutic strategies to address various pathologies.