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

The Transthyretin – Retinol-binding protein 4 (TTR-RBP4) complex is a vital transport assembly in human plasma responsible for the systemic delivery of Vitamin A (retinol). Transthyretin, a homotetrameric protein, binds to the smaller Retinol-binding protein 4 to increase its effective molecular weight, thereby preventing the rapid renal filtration and excretion of RBP4 and its retinol cargo (Source: UniProt P02766, P02753). This complex has gained significant attention as a therapeutic target because elevated levels of RBP4 are linked to the development of insulin resistance and Type 2 diabetes (Source: Nature, PMID: 16362046). Furthermore, in the context of ophthalmology, the complex is targeted to reduce the influx of retinol into the visual cycle, which helps mitigate the accumulation of toxic lipofuscin precursors in diseases like Stargardt disease and dry age-related macular degeneration (Source: Journal of Biological Chemistry, PMID: 25100772). Pharmacological strategies involve using small molecules, such as fenretinide or non-retinoid antagonists like tinlarebant, to disrupt the TTR-RBP4 interaction. This disruption facilitates the renal clearance of RBP4, effectively lowering circulating retinol levels and providing therapeutic benefits in metabolic and degenerative conditions.

Other names

TTR-RBP4 complexPrealbumin-Retinol binding protein complexTransthyretin-RBP complexTTR-RBP complex

Disruption of the protein-protein interaction between Transthyretin and Retinol-binding protein 4 to promote renal excretion of RBP4 and lower systemic retinol levels.