Congenital hereditary retinoschisis, also known as X-linked juvenile retinoschisis (RS), is a bilateral vitreoretinal disorder that develops early in life. It is a leading cause of juvenile macular degeneration in male but clinically affected female heterozygote has also been reported. The condition is characterized by the macular degeneration and splitting (schisis) of the neural retina leading to the reduced visual acuity and impaired synaptic transmission in childhood. The clinical picture of the disorder not only varies from family to family but also among affected family members. Female carriers cannot be identified by clinical means alone. The disorder is fully penetrant, has an estimated prevalence of 1 in 15-30,000 and accounts for almost all congenital RS cases. Linkage analyses have mapped the gene on chromosome Xp22.1 and a causative gene (RS1) encoding 24 kDa discoidin domain containing protein (retinoschisin) was isolated. The gene is expressed in photoreceptor and bipolar cells. It is implicated in cellular adhesion and cell – cell interactions. The retinoschisin is a secreted protein and functions as a homo-octamer complex. Over a 100 alteration consisting of missense, frameshift, deletion, insertion, splice site and truncation in the RS1 gene has been identified and found to be associated with RS. Females homozygous for mutations in the RS1 gene manifest a similar clinical phenotype to that of affected males. In order to understand the pathophysiology of the disorder, three mouse models have been developed. These mice exhibited very similar clinical pathology to that of the human disease Additionally, they demonstrated the existence of genetic modifying factors that determine the severity and penetrance of the disorder. Recent gene transfer experiments using these mouse models demonstrated a long time rescue from retinal degeneration implicating that gene replacement therapy may be possible for patients in the future.