Crx has been implicated in three photoreceptor diseases that result in human blindness, cone-rod dystrophy2, Leber's congenital amaurosis, and retinitis pigmentosa (for review, see [53]). The cone-rod dystrophies (CRDs) are characterized by loss of cone-mediated vision in the first decade of life or later, with concomitant or subsequent loss of rod-mediated vision [54]. Conversely, RP is notable for initial loss of rod function, followed by loss of cone-mediated vision [55]. The majority of known genes responsible for human genetic blindness, encode proteins expressed almost exclusively, or exclusively, in photoreceptors, particularly in the outer segment [35]. Many of these proteins are required for phototransduction or outer segment structure. The mechanisms whereby mutations in rod-specific genes, such as rhodopsin, lead eventually to cone degeneration in RP remain obscure. Mutations in Crx were the first, and still one of a very few examples of a transcription factor mutation leading to photoreceptor disease.