Lipoxygenase homology domain-containing protein 1 (LOXHD1) (LOXHD1)

Lipoxygenase homology domain-containing protein 1 (LOXHD1) is a scaffold protein primarily expressed in the mechanosensory hair cells of the inner ear. It is composed of 15 polycystin-1, lipoxygenase, and alpha-toxin (PLAT) domains, which are thought to mediate membrane-protein or protein-protein interactions critical for the structural integrity of stereocilia. LOXHD1 is localized along the length of the stereocilia and plays a vital role in the mechanotransduction process, which converts sound-induced vibrations into electrical signals for the brain. Mutations in the LOXHD1 gene are a leading cause of autosomal recessive non-syndromic hearing loss, specifically the DFNB77 phenotype, which can present as congenital or late-onset progressive deafness. Due to its essential role in auditory function and the monogenic nature of DFNB77, LOXHD1 has become a primary target for gene therapy. Current therapeutic approaches focus on using adeno-associated virus (AAV) vectors to deliver a wild-type copy of the LOXHD1 gene directly into the cochlea to restore or preserve hearing in affected individuals.

Other names

DFNB77LH2D1Lipoxygenase homology domain 1PLAT domain-containing protein 1

Gene replacement therapy to restore functional LOXHD1 protein in mechanosensory hair cells