PRDX1 is a thiol-specific peroxidase that catalyzes reduction of hydrogen peroxide and organic hydroperoxides, protecting cells from oxidative stress 1. Beyond its canonical peroxidase function, PRDX1 acts as a molecular chaperone and signaling regulator with broad disease relevance. Mechanistically, PRDX1 operates through multiple pathways. It inhibits TRAF6 ubiquitin-ligase activity, suppressing NF-κB and autophagy activation in TLR4 signaling 2. PRDX1 stabilizes NRF2 by binding Cullin-3 to prevent its ubiquitination, activating antioxidant gene expression including GPX4 3. Notably, its peroxidase activity can be inhibited by palmitic acid or enhanced by rosmarinic acid through stabilization of its peroxidatic cysteine 1. PRDX1 dysfunction contributes to multiple diseases. In nonalcoholic steatohepatitis, palmitic acid-induced inhibition of PRDX1 peroxidase activity exacerbates pathology through STAT signaling and mitochondrial oxidative damage 1. In hepatocellular carcinoma, ZNF207-mediated lactylation of PRDX1 at lysine 67 promotes ferroptosis evasion and regorafenib resistance via NRF2 activation 4. PRDX1 overexpression supports colorectal cancer progression through ferroptosis suppression 3. Clinically, PRDX1 emerges as a therapeutic target. Small molecules targeting PRDX1 (celastrol, ainsliadimer A, rosmarinic acid) suppress colorectal cancer proliferation and activate p53 signaling 56. In cardiac hypertrophy, TRIM16-mediated suppression of PRDX1 phosphorylation attenuates pathological remodeling 7.