USH2A encodes usherin, a component of the USH2 complex essential for sensory function. In the inner ear, USH2A maintains hair bundle ankle links that connect developing stereocilia in cochlear hair cells, supporting hearing function 1. In retinal photoreceptors, it maintains the periciliary membrane complex, regulating intracellular protein transport and supporting vision 2. USH2A mutations cause two clinically distinct inherited retinal diseases: Usher syndrome type 2 (USH2), characterized by combined deafness and progressive blindness, and non-syndromic retinitis pigmentosa (RP) with vision loss alone 3. Genotype-phenotype analysis reveals that biallelic truncating variants correlate with earlier symptom onset and more severe visual decline than missense variants 4. USH2A is among the most frequently mutated genes in inherited retinal disease globally, accounting for 11-15.75% of molecularly diagnosed IRD cases 54. Population-specific hotspot variants predominate, including p.Cys934Trp in non-syndromic RP and c.8559-2A>G in USH2 67. CNV detection increases diagnostic yield, identifying pathogenic variants in an additional 8.8% of IRD patients 8. These findings enable precise genetic diagnosis and inform therapeutic development strategies.