MARVELD2 encodes tricellulin, a tricellular tight junction protein essential for epithelial barrier function. 1 The protein localizes to tricellular junctions where three epithelial cells meet, playing a critical role in sealing intercellular spaces. 2 In the inner ear, MARVELD2 is required for normal hearing by maintaining separation of endolymphatic and perilymphatic compartments and ensuring hair cell survival in the organ of Corti. 1 Loss of MARVELD2 function causes DFNB49, autosomal recessive non-syndromic hearing loss, representing approximately 1.5% of prelingual deafness in Pakistani populations and the second most common cause in Czech Roma. 1 Pathogenic variants include frameshift mutations and splice site alterations that impair protein stability and localization. 3 4 Beyond hearing, MARVELD2 mutations affect tissues with specialized barrier functions; mouse models exhibit additional defects in salivary glands, thyroid, and olfactory epithelium, though human syndromic manifestations remain unreported. 1 Recent evidence reveals MARVELD2's role in salivary gland barrier dysfunction in Sjögren's syndrome, where tricellulin downregulation occurs via JAK/STAT1/miR-145 signaling. 5 MARVELD2 represents a promising candidate for vestibular disorder research given its cochlear and vestibular tissue expression. 6