Emerging role of T3-binding protein μ-crystallin (CRYM) in health and disease

Thyroid hormones are essential metabolic and developmental regulators that exert a huge variety of effects in different organs. Triiodothyronine (T3) and thyroxine (T4) are synthesized in the thyroid gland and constitute unique iodine-containing hormones that are constantly regulated by a homeostatic feedback mechanism. T3/T4 activity in cells is mainly determined by specific transporters, cytosolic binding proteins, deiodinases (DIOs), and nuclear receptors. Modulation of intracellular T3/T4 level contributes to the maintenance of this regulatory feedback. μ-Crystallin (CRYM) is an important intracellular high-affinity T3-binding protein that buffers the amount of T3 freely available in the cytosol, thereby controlling its action. In this review, we focus on the molecular and pathological properties of CRYM in thyroid hormone signaling, with emphasis on its critical role in malignancies.