The role of the primary cilium in thyroid function and dysfunction with implications for thyroid disease

The thyroid gland is a unique endocrine organ, composed of morpho-functional units called thyroid follicles, which are responsible for thyroid hormone (TH) biosynthesis, an iodination process demanding a highly oxidative yet protected environment. Despite primary cilium (PC) being observed in the thyroid gland more than a century ago, its precise role in thyroid activity remains rather unexplored. Given its strategic position at the apical surface of follicular epithelium, projecting into the lumen, PCs are crucial for the regulation of TH biosynthetic processes. Consequently, changes in thyroid function, either physiological or pathological, are reflected in PC characteristics. Similarly, defects in ciliogenesis are expected to lead to different pathological thyroid alterations. This review summarizes the current understanding of PC's involvement in regulating normal thyroid activity and its modifications in functional and neoplastic thyroid diseases. Particular focus will be given to the notable loss of PCs in certain types of thyroid cancer and the promising potential of their restoration as a tumor suppressor strategy in thyroid tumorigenesis.