Usher syndrome type-2A protein (Usherin) (USH2A)

Usher syndrome type-2A protein, commonly known as Usherin, is a large transmembrane protein essential for the structural integrity and functional maintenance of sensory cells in the inner ear and retina (UniProt O75445). It is a major component of the protein complex located at the base of the stereocilia in cochlear hair cells and the connecting cilium of photoreceptors, where it facilitates cell-cell adhesion and intracellular signaling (NCBI Gene 7399). Mutations in the USH2A gene are the most frequent cause of Usher syndrome, a genetic disorder characterized by congenital hearing loss and progressive vision loss due to retinitis pigmentosa (PubMed PMID: 10332031). Because of its critical role in sensory maintenance, Usherin has become a primary target for genetic and RNA-based therapies. Current clinical efforts, such as the development of the antisense oligonucleotide Ultevursen, focus on correcting splicing defects like exon 13 mutations to restore functional protein expression in the retina (ProQR Therapeutics). The therapeutic challenge remains significant due to the protein's massive size and the need for precise delivery to specialized sensory tissues.

Other names

UsherinUSH2Protein USH2AUsher syndrome type IIa protein

Antisense oligonucleotide-mediated exon skipping to restore the reading frame or bypass pathogenic mutations in the USH2A pre-mRNA transcript.