mu-crystallin, a NADPH-dependent T(3)-binding protein in cytosol

Thyroid hormone action is initiated through nuclear thyroid hormone receptors (TRs). Before the discovery of these nuclear receptors, possible major binding sites for thyroid hormones were thought to be cytosolic owing to high thyroid hormone-binding activity in crude cytosolic fractions. Several cytosolic thyroid hormone-binding proteins have been identified, including reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent 3,5,3'-triiodo-L-thyronine (T(3))-binding protein, also known as mu-crystallin, which was initially cloned as the ortholog of bacterial ornithine cyclodeaminase. The expression of mu-crystallin is developmentally regulated and cell-type specific. Recently, patients with nonsyndromic deafness were reported to have point mutations in the mu-crystallin gene. Cytosolic thyroid hormone-binding proteins, especially mu-crystallin, have roles in adaptation to environmental alterations by thyroid hormone, which might have a role in hearing function.