Cellular retinol-binding protein (CRBP)

Cellular retinol-binding proteins (CRBPs) are a family of low-molecular-weight (approx. 15-16 kDa) cytosolic proteins belonging to the fatty acid-binding protein (FABP) superfamily [2.2.2, 2.4.2]. They serve as essential intracellular chaperones for retinol (vitamin A) and its metabolite retinal, protecting these hydrophobic molecules from the aqueous cellular environment and directing them to specific enzymes for the synthesis of retinoic acid or storage as retinyl esters [2.3.1, 2.3.3]. CRBP1 is widely expressed and critical for maintaining retinoic acid homeostasis; its downregulation via epigenetic silencing is a frequent event in various cancers, including breast and ovarian cancer, where it acts as a tumor suppressor by promoting cell differentiation [2.3.5, 3.1.2]. CRBP2 is primarily localized in the small intestine, where it facilitates the absorption and metabolic channeling of dietary vitamin A and has recently been linked to the regulation of monoacylglycerol levels and metabolic health [2.2.1, 2.2.3]. Due to their central role in retinoid signaling, CRBPs are emerging as therapeutic targets; for instance, CRBP1 inhibition is being explored to treat ocular diseases like Stargardt disease by slowing the accumulation of toxic bis-retinoids [3.2.1, 3.2.3]. Additionally, the reactivation of CRBP1 expression or the use of synthetic retinoids that interact with these proteins represents a potential strategy in oncology and metabolic disease management [2.4.1, 3.1.2].

Other names

Retinol-binding protein 1Retinol-binding protein 2Retinol-binding protein 5Retinol-binding protein 7CRBP1CRBP2CRBP3CRBP4CRBP-ICRBP-IICRBP-IIICRBP-IVRBP1RBP2RBP5RBP7

Cellular retinol-binding proteins (CRBPs) function as intracellular chaperones that sequester retinol and retinal, protecting them from non-specific oxidation and delivering them to specific metabolic enzymes such as lecithin:retinol acyltransferase (LRAT) and retinaldehyde dehydrogenases (RALDHs) [2.3.1, 2.3.3]. This process regulates the bioavailability of all-trans retinoic acid (atRA), which subsequently activates nuclear retinoic acid receptors (RARs) to control gene expression related to cell differentiation and proliferation [2.3.4, 3.1.5]. Pharmacological inhibitors like abnormal cannabidiol (abn-CBD) target CRBP1 to modulate retinoid flux in the visual cycle for treating retinal degeneration [3.2.1, 3.2.3], while demethylating agents can be used to reactivate CRBP1 expression in silenced cancer cells to restore differentiation signaling [3.1.2].