Retinol-binding protein 4–transthyretin complex (RBP4–TTR complex)

The Retinol-binding protein 4–transthyretin (RBP4–TTR) complex is a vital transport assembly in human plasma responsible for the systemic delivery of vitamin A (retinol) (Source: UniProt P02753, P02766). RBP4, a 21 kDa member of the lipocalin family, binds retinol in the liver and subsequently associates with TTR, a 55 kDa homotetrameric protein (Source: PubMed PMID: 10747963). This association increases the overall molecular size of the complex, effectively preventing the rapid renal filtration and clearance of the relatively small RBP4 protein (Source: PubMed PMID: 22435004). Beyond its physiological role in nutrient transport, the RBP4–TTR complex has emerged as a significant therapeutic target in metabolic and ophthalmological disorders. Elevated levels of RBP4 are strongly associated with insulin resistance, obesity, and type 2 diabetes, where it acts as an adipokine that impairs glucose uptake in muscle and increases hepatic glucose production (Source: PubMed PMID: 16778894). In the context of retinal diseases such as Stargardt disease and dry age-related macular degeneration, the complex facilitates the delivery of retinol to the retinal pigment epithelium, where excessive vitamin A can lead to the accumulation of toxic lipofuscin bisretinoids (Source: PubMed PMID: 25135908). Pharmacological strategies often focus on small molecules that disrupt the RBP4–TTR interaction or displace retinol from RBP4, thereby promoting the renal excretion of RBP4 and lowering systemic retinol levels to mitigate metabolic dysfunction or retinal toxicity (Source: Belite Bio, ClinicalTrials.gov).

Other names

RBP-TTR complexRetinol-binding protein-prealbumin complexRBP4-TTR holo-complexRetinol-binding protein 4-transthyretin complex

Disruption of the RBP4-TTR complex or inhibition of retinol binding to RBP4, leading to increased renal clearance of RBP4 and subsequent reduction in circulating retinol levels (Source: PubMed PMID: 22435004, 30215183).