Retinol-binding protein 4 (RBP4) (RBP4)

Retinol-binding protein 4 (RBP4) is the specific carrier for retinol (vitamin A) in the blood, responsible for transporting it from liver stores to peripheral tissues (UniProt P02753). In the circulation, RBP4 exists primarily in a complex with transthyretin (TTR), a 1:1 molar ratio interaction that increases the molecular weight of RBP4 to prevent its glomerular filtration and subsequent renal clearance (PubMed: 22135311). RBP4 has gained significant attention as an adipokine; elevated serum levels are strongly correlated with insulin resistance, obesity, and type 2 diabetes (PubMed: 16778882). In the context of ophthalmology, RBP4 is a validated target for treating dry age-related macular degeneration and Stargardt disease. By using small-molecule antagonists to disrupt the RBP4-TTR complex, circulating retinol levels are reduced, which in turn limits the accumulation of lipofuscin bisretinoids like A2E in the retinal pigment epithelium (PubMed: 25100212). Therapeutic candidates like Tinlarebant and Fenretinide aim to lower these levels to preserve visual function (ClinicalTrials.gov: NCT05244304).

Other names

Serum retinol-binding proteinPlasma retinol-binding proteinRBPPRBPRetinol-binding protein 4, plasma

RBP4-targeted therapies primarily function as non-retinoid antagonists or ligands that bind to the retinol-binding pocket of RBP4. This binding induces a conformational change or sterically hinders the interaction between RBP4 and transthyretin (TTR). The disruption of the RBP4-TTR complex reduces the effective molecular size of RBP4, leading to its rapid excretion by the kidneys. This results in a systemic reduction of both RBP4 and its ligand, retinol, thereby reducing the delivery of vitamin A to the visual cycle or improving systemic metabolic profiles (PubMed: 24464926, PubMed: 29335261).