In this study, we have explored the long-term USH2A pathophysiology in humans and examined the molecular defects underlying USH2A-associated retinal degeneration in a novel zebrafish mutant [ush2au507; c.2131_2203+73delinsCGGCGG; p.(Ala711fs*), exon 12; transcript ID: XM_009293147.3] and the previously published ush2armc1 mutant, to further improve our understanding of the molecular pathology underlying the disease and to identify potential outcome measures for assaying a response to emerging therapeutics in both preclinical and clinical studies. Here, USH2A is linked to retinal degeneration.