TXNRD1 (thioredoxin reductase 1) is a cytosolic selenoprotein that functions as a key regulator of cellular redox homeostasis and inflammatory responses. The enzyme catalyzes the reduction of thioredoxin and other substrates using NADPH, playing essential roles in antioxidant defense 1. TXNRD1 is regulated by the NRF2 transcription factor and serves as a robust biomarker of NRF2 signaling activity across multiple cell types 2. Beyond its enzymatic function, TXNRD1 acts as a critical mediator of senescence-associated inflammation through direct interaction with the cGAS-STING innate immune pathway, independent of its reductase activity 3. In disease contexts, TXNRD1 demonstrates complex roles: it promotes cancer cell survival by conferring ferroptosis resistance through antioxidant mechanisms 14, while its upregulation in COPD contributes to cigarette smoke-induced inflammation and oxidative stress via the Nrf2/HO-1 pathway 5. TXNRD1 also participates in retrograde mitochondrial-nuclear signaling in retinal pigment epithelial cells, influencing cellular reprogramming in age-related macular degeneration 6. Therapeutically, TXNRD1 inhibition shows promise for treating inflammaging, cancer, and metabolic disorders, making it an attractive target for multiple age-related diseases 31.