Tricellulin (MARVELD2)

Tricellulin (MARVELD2) is a membrane protein located at tricellular tight junctions—specialized connections where three epithelial cells meet. It plays a crucial role in forming and maintaining epithelial barriers, particularly in the inner ear’s organ of Corti, where its function is essential for normal hearing by keeping the endolymphatic and perilymphatic spaces separated. Biallelic mutations in MARVELD2 cause autosomal recessive non-syndromic deafness type DFNB49. Tricellulin is a member of the tight junction–associated MARVEL protein (TAMP) subfamily, related to occludin and marvelD3, with nonredundant roles in epithelial physiology. It is grouped with occludin and marvelD3 as the TAMP family of tight junction proteins, which are critical for regulating paracellular barrier function in epithelial tissues. Despite similarities, each family member, including tricellulin, plays unique and non-redundant roles at different cell–cell junction regions. MARVELD2 is essential for the integrity of tight junctions, particularly at tricellular contacts. Loss of function is linked with hereditary sensorineural deafness without major syndromic features. While its disruption is disease-causing, there is no evidence that MARVELD2 is a current target for therapeutic drugs, nor are there established mechanisms of action or interacting drugs for this protein. Its genetic variants act as biomarkers for DFNB49-related deafness. Currently, no drugs are known to target this protein directly. Safety concerns are centered on gene loss or mutation leading to congenital hearing loss, rather than therapeutic intervention.

Other names

MARVEL domain-containing protein 2MARVELD2TricellulinTRICDFNB49MRVLDC2FLJ30532TricMARVD2tricellulin