Humans are afflicted with a large and heterogenous group of inherited blinding diseases. Most share the common histopathological feature of photoreceptor-cell death. The prototypical disease in this group is retinitis pigmentosa (RP), with the clinical phenotype of progressive night blindness and tunnel vision, advancing to complete visual loss in later life. As a group, human retinal degenerations are characterized by both allelic and nonallelic heterogeneity. For example, mutations in multiple unrelated genes may cause the RP phenotype, whereas different alleles of a single gene, such as RDS, may cause clinically disparate retinal diseases. Many genes have been identified as responsible for human retinal degeneration. The genes for several proteins in the visual transduction pathway have been implicated, including those for rhodopsin (reviewed in Rao and Oprian 1996; Shastry 1997), transducin (Dryja et al. 1996), both a-and b-catalytic subunits of cGMP-phosphodiesterase (PDE)(Huang et al. 1995; Mc-Laughlin et al. 1995), the cGMP-gated cation channel (Dryja et al. 1995), rhodopsin kinase (Yamamoto et al. 1997), arrestin (Fuchs et al. 1995), and guanylate cyclase (Perrault et al. 1996). Mutations in genes for other photoreceptor-specific proteins, including rds/peripherin (reviewed in Shastry 1997), rom1 (Kajiwara et al. 1994), rim protein (RmP)(Allikmets 1997; Allikmets et al. 1997; Azarian and Travis 1997), and crx, a newly discovered otx-like homeodomain protein (Freund et al. 1997), have been reported to cause retinal degeneration. Photoreceptor-cell death also may be caused by mutations in genes expressed in the overlying retinal pigment epithelium (RPE), including the genes for cellular retinaldehyde binding protein (CRALBP)(Maw et al. 1997)