model for understanding the largest receptor family in the human genome, the G protein-coupled receptors, and because defects in the rhodopsin gene are the most common cause of the most common inherited blinding disease, retinitis pigmentosa. Rhodopsin Mutation The human rhodopsin gene is the locus for numerous alleles linked to the neurodegenerative disease retinitis pigmentosa. Mutations in the rhodopsin gene account for 25% to 30% (30% to 40% according to ) of all cases of autosomal dominant retinitis pigmentosa (ADRP). Over 100 distinct mutations in the light-sensing molecule rhodopsin are known to cause (adRP). Most of these mutations are missense mutations affecting single amino acid residues in the rhodopsin protein. These mutations affect rhodopsin transport to the outer segments of rod photoreceptor cells, rhodopsin folding, and rhodopsin endocytosis. Mutations in the human rhodopsin that affect its folding, trafficking and activity are the most commonly encountered causes of retinal degeneration in patients affected by RP. A single base-substitution mutation of codon 23 of the rhodopsin gene in which proline is changed to histidine (Pro23His) in the human opsin gene accounts for the largest fraction of rhodopsin mutations observed in the United States and is the most common cause of ADRP in American patients. In 1990, the Pro23His mutation of the rhodopsin gene was reported as the first mutation associated with RP. This mutation has been described only in the United States, where it continues to be the most commonly described gene defect in RP. The phenotype of the RP associated with the P23H mutation is characteristically relatively mild but variable. Multiple studies have demonstrated that the degree of severity of a given mutation in the rhodopsin gene is based in large part on its position in the rhodopsin molecule—intradiscal, transmembrane, or cytoplasmic. Intradiscal mutations tend to be less severe, whereas mutations affecting cytoplasmic domains and retinol binding sites tend to be very severe. The severity of cytoplasmic mutations affecting maintenance of photoreceptor cell polarity, such as those at the C-terminus (sorting signal of rhodopsin) may result from inappropriate intracellular transport of the molecule. Some research has described transgenic mouse mutants that cause degeneration by prolonged activation of the phototransduction cascade. In this research null mutations in the rhodopsin kinase and arrestin genes, each of which plays a role in terminating rhodopsin activity, caused light-dependent retinal degeneration. Rhodopsin C-terminal mutations A fraction of rhodopsin mutations alter the C-terminal tail of the protein,