SELENOW (selenoprotein W) is a ~9 kDa selenocysteine-containing protein that functions as a glutathione-dependent antioxidant involved in redox homeostasis 1. The protein is highly expressed in muscle, heart, brain, and liver tissues 2, as well as in intestinal epithelial cells, endothelial cells, and stem cells 3. Mechanistically, SELENOW regulates multiple cellular pathways. In hepatocytes, it interacts with pyruvate kinase M2 (PKM2) to modulate metabolic reprogramming, triggering mitochondrial apoptosis and pyroptosis through ROS accumulation and NLRP3 inflammasome activation 4. In the intestinal epithelium, SELENOW promotes epithelial repair through EGFR and YAP1 signaling 3. In neurons, SELENOW promotes tau degradation via the ubiquitin-proteasome system by competing with Hsp70 5. In bone, SELENOW is downregulated by RANKL signaling and its overexpression enhances osteoclastogenesis through NF-κB and NFATc1 translocation 67. Clinically, SELENOW downregulation associates with protective effects in ulcerative colitis and reduced tau pathology in Alzheimer's disease 35. Conversely, elevated SELENOW expression contributes to pathological bone loss in multiple myeloma and NAFLD progression 47. These findings suggest SELENOW's tissue-specific roles in disease pathogenesis.