CLDN14

CLDN14 (Claudin-14) is a protein encoded by the CLDN14 gene in humans. It belongs to the claudin superfamily, a group of integral membrane proteins that are crucial components of tight junctions. Tight junctions are multiprotein complexes that create paracellular barriers, regulating the passage of ions and small molecules between epithelial and endothelial cells. They play a critical role in maintaining cell polarity, preventing the diffusion of membrane proteins, and establishing the overall barrier function of tissues.

Specifically, Claudin-14 is primarily expressed in the inner ear and kidney. In the inner ear, it is found in supporting cells within the cochlea. Its expression is linked to hearing sensitivity. Mutations in the CLDN14 gene are a significant cause of autosomal recessive non-syndromic hearing loss, specifically DFNB29. These mutations typically disrupt the structure or function of the Claudin-14 protein, interfering with its role in maintaining the ionic balance and integrity of the inner ear, ultimately leading to hearing impairment.

In the kidney, Claudin-14 is expressed in the thick ascending limb of the loop of Henle, where it affects calcium and magnesium reabsorption. It decreases paracellular permeability to calcium and magnesium. The precise regulatory mechanisms controlling Claudin-14 expression in the kidney, and the implications of its dysfunction in renal disorders, are still under investigation. However, its involvement in mineral ion transport makes it a potentially important factor in conditions such as hypercalciuria or hypomagnesemia.

Further research is ongoing to fully elucidate the precise roles of Claudin-14 in different tissues, its regulatory mechanisms, and its involvement in various diseases beyond hearing loss. Understanding its function is critical for developing potential therapeutic interventions for related conditions.