Thioredoxin reductases are selenoproteins that are critical for maintaining cellular redox balance and eliminating reactive oxygen species (ROS). There are three known mammalian thioredoxin reductases: TRXR1/TXNRD1 (cytosolic), TRXR2/TXNRD2 (mitochondrial), and TRXR3/TXNRD3 (testis-specific). TRXR2 may function to protect against tumor necrosis factor-? (TNF-?)-mediated ROS generation. TRXR2 is critical for normal heart development and function. TRXR2 KO mice experience embryonic lethality, while mitochondrial dysfunction seen in heart-specific TRXR2 KO mice results in congestive heart failure. In humans, certain rare mutations in TRXR2 have been linked to dilated cardiomyopathy. A recent study in the EPIC-Heidelberg cohort shows that serum selenium levels, in concert with certain SNPs in TRXR2 and other selenoproteins, can influence prostate cancer risk.