GLRX3 (glutaredoxin 3) is a cytosolic iron-sulfur (Fe-S) cluster assembly factor that functions as a critical regulator of cellular iron homeostasis and redox balance. Primary function: GLRX3 forms [2Fe-2S]-bridged complexes with BOLA2 to facilitate [2Fe-2S] cluster insertion into cytosolic proteins 1, playing essential roles in hemoglobin maturation and iron metabolism regulation 2. Unlike typical thioredoxins, GLRX3 lacks catalytic activity but maintains low intracellular ROS levels through its antioxidant function 3. Mechanism: GLRX3 coordinates iron availability signaling through conserved interactions with GMP synthase and participates in stress response pathways, contributing to cellular lifespan extension 4. Disease relevance: GLRX3 is significantly dysregulated in multiple cancer types. In oral squamous cell carcinoma, elevated GLRX3 promotes migration and invasion via Notch-dependent epithelial-mesenchymal transition and ROS suppression 3. In hepatocellular carcinoma, GLRX3 facilitates tumor proliferation and immune evasion 2. In pancreatic ductal adenocarcinoma, GLRX3 regulates cancer stem cell properties through Met/PI3K/AKT signaling 5. Clinical significance: GLRX3 serves as a promising diagnostic and prognostic biomarker, with serum GLRX3 showing 80% sensitivity and 100% specificity for pancreatic cancer diagnosis 5. Additionally, GLRX3 protects against atherosclerosis through miRNA-mediated regulation 6.