In this review, we reviewed the literature to describe the morphofunctional differences in IRD patients with genetic mutations that are common to them, such as RP, CSNB, BBS and USH, which are related to the RPE65 mutation, in order to identify clinical and diagnostic biomarkers, useful for stratifying patients in need of early therapy to increase diagnostic and treatment chances for gene therapy, which, to date, is the only treatment that appears to slow photoreceptor damage. The gene discussed is RPE65; the disease is Usher syndrome.