The adjacent selenocysteine (Sec) and cysteine (Cys) residues in the C-terminus of mammalian TRs are required for reductase activity when Trx is the substrate; however, Sec-deficient TR1 may have biochemical [15] and biological [16] activities distinct from Sec-sufficient TR1 that may be relevant in cancer or other disease. Here, TXN is linked to cancer.