The cellular retinaldehyde-binding protein (CRALBP) 1 is thought to play a fundamental role in vitamin A metabolism in the retina and retinal pigment epithelium (RPE). Notably, mutations in the human CRALBP gene can result in autosomal recessive retinitis pigmentosa (1). In vitro CRALBP serves as a substrate carrier protein for enzymes of the mammalian visual cycle, modulating whether 11-cis-retinol (11-cis-Rol) is stored as an ester in the RPE or oxidized by 11-cis-Rol dehydrogenase to 11-cis-retinal (11-cis-Ral) for visual pigment regeneration (2). In the RPE and Mü ller cells of the retina, CRALBP carries endogenous 11-cis-retinoids, the isomers of vitamin A utilized for phototransduction. However, CRALBP is not always associated with a retinoid ligand and more than one physiological role for the protein appears likely (3). The protein is also present in ciliary body, cornea, pineal gland, optic nerve, brain, transiently in iris, but not in the rod and cone photoreceptors. CRALBP is expressed in developing retina and RPE before the tissues contain 11-cis-retinoids or the enzyme responsible for generating 11-cis-retinoids (3). Apparently the protein serves functions unrelated to visual pigment regeneration in brain and tissues not involved in the visual cycle and may bind ligands other than retinoids.CRALBP was first detected in retina about 20 years ago and shown to carry 11-cis-Rol and 11-cis-Ral as endogenous ligands (4,5). Structure function studies have defined ligand stereoselectivity and photosensitivity (6), developed a topological and epitope map (7), established in vitro evidence for a substrate carrier function in RPE (8, 9) and produced human recombi-