PRDX4 is a thiol-specific peroxidase that catalyzes reduction of hydrogen peroxide and organic hydroperoxides, functioning as the only known secretory member of the peroxiredoxin family 1. It operates in both intracellular compartments, particularly the endoplasmic reticulum, and extracellular space to protect against oxidative stress 1. Beyond antioxidant defense, PRDX4 regulates cellular redox signaling and hydrogen peroxide-mediated signaling events, including modulation of NF-κB activation 2. Mechanistically, PRDX4 functions through multiple pathways. In alveolar macrophages, oligomeric PRDX4 disrupts PTEN homodimer formation via critical cysteine residues (Cys124 and Cys245), thereby enhancing AKT/NF-κB signaling and macrophage activation 3. PRDX4 also interacts with TXNDC5 in gastric cancer and participates in neutrophil degranulation signaling pathways 4. Additionally, PRDX4 mediates endoplasmic reticulum-Golgi protein trafficking, promoting antioxidant capacity and protein translation in T cells 5. Clinically, PRDX4 is significantly upregulated in multiple cancers including breast, prostate, ovarian, colorectal, and lung cancer, contributing to tumorigenesis, therapeutic resistance, and metastasis 2. In silicosis and idiopathic pulmonary fibrosis, elevated PRDX4 promotes aberrant macrophage activation and fibrosis progression 3. PRDX4 also protects against metabolic syndrome components including atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease by reducing oxidative stress 1. These diverse roles suggest PRDX4 as a promising therapeutic target across inflammatory and malignant diseases.