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

The Transthyretin-Retinol-binding protein 4 (TTR-RBP4) complex is a critical transport system in human plasma, primarily responsible for the systemic distribution of Vitamin A (retinol) and the secondary transport of thyroid hormones like thyroxine (T4) [3, 8]. Transthyretin, historically known as prealbumin, is a homotetrameric protein synthesized mainly in the liver and choroid plexus [5, 8]. It forms a stable complex with Retinol-binding protein 4 (RBP4), a 21 kDa lipocalin that carries a single molecule of retinol [2, 9]. This protein-protein interaction is essential for preventing the rapid renal filtration of the small RBP4 protein, thereby maintaining homeostatic levels of circulating retinol [5, 16]. Therapeutically, both components of the complex are significant targets. Transthyretin is the focus of treatments for TTR amyloidosis (ATTR), where stabilizers like Tafamidis prevent the tetramer from dissociating into amyloidogenic monomers [1, 6]. RBP4 is targeted in ocular conditions such as Stargardt disease and dry age-related macular degeneration (AMD); RBP4 antagonists like Tinlarebant disrupt the TTR-RBP4 interaction, leading to the clearance of RBP4 and a subsequent reduction in serum retinol, which limits the formation of toxic retinal bisretinoids [5, 7]. Additionally, the complex serves as a sensitive clinical biomarker for assessing nutritional status and liver synthetic function, as levels of both proteins drop rapidly during protein-calorie malnutrition or systemic inflammation [4, 12, 15].

Other names

Prealbumin-Retinol-binding protein complexTTR-RBP4 complexThyroxine-binding prealbumin-RBP complexTransthyretinRetinol-binding protein 4PrealbuminRBP4Thyroxine-binding prealbumin (TBPA)

Transthyretin tetramer stabilization (e.g., Tafamidis) [1, 6]; Retinol-binding protein 4 antagonism and complex dissociation (e.g., Tinlarebant, Fenretinide) [3, 7]; Inhibition of transthyretin synthesis via RNA interference or antisense oligonucleotides (e.g., Patisiran, Inotersen) [8].