Usherin (USH2A) (USH2A)

Usherin is a large transmembrane protein encoded by the USH2A gene, primarily localized to the basement membranes of the inner ear and the connecting cilia of retinal photoreceptors (UniProt O75445). It plays a critical role in the structural integrity and functional maintenance of these sensory cells by forming a protein complex with other Usher syndrome-related proteins like ADGRV1 and whirlin (PubMed: 21665994). Mutations in USH2A are the most common cause of Usher syndrome, characterized by congenital hearing loss and progressive vision loss due to retinitis pigmentosa (NIH/GARD). Because the USH2A gene is exceptionally large, traditional gene replacement using standard AAV vectors is challenging, leading to the development of alternative strategies such as antisense oligonucleotides (ASOs) and dual-vector systems (PubMed: 31513941). Current therapeutic efforts, such as the ASO ulbevorsen (QR-421a), focus on exon skipping to restore protein function in patients with specific mutations (ProQR Therapeutics). Understanding the usherin functional complex is vital for developing precision medicines aimed at preserving sensory function in affected individuals.

Other names

Usher syndrome type-2A proteinUSH2AUsherin functional complexUsher syndrome type IIa protein

Antisense oligonucleotide-mediated exon skipping to restore the reading frame; Gene replacement therapy using viral vectors; CRISPR-based gene editing to correct mutations.