Stimulated by retinoic acid 6 – Retinol-binding protein 4 – Retinol complex (STRA6-RBP4-Retinol)

The Stimulated by retinoic acid 6 (STRA6) – Retinol-binding protein 4 (RBP4) – Retinol complex is a pivotal molecular assembly that governs the cellular uptake of vitamin A from the bloodstream. STRA6 is a multi-pass transmembrane protein that serves as the high-affinity cell-surface receptor for RBP4, the primary carrier of retinol in circulation (UniProt Q9BX79). Upon binding the RBP4-retinol complex, STRA6 facilitates the transport of retinol across the cell membrane, a process essential for the visual cycle in the retinal pigment epithelium and for maintaining vitamin A homeostasis in various tissues (Chen et al., 2016, Science). Beyond transport, the interaction between RBP4 and STRA6 triggers intracellular signaling pathways, specifically the JAK2/STAT5 cascade, which has been linked to the development of insulin resistance in obesity and type 2 diabetes (Berry et al., 2012, Cell). Consequently, elevated levels of RBP4 are considered a biomarker and a causative factor in metabolic dysfunction (Graham et al., 2006, NEJM). In the eye, excessive retinol uptake via this complex leads to the accumulation of toxic lipofuscin bisretinoids, which are implicated in the pathogenesis of Stargardt disease and age-related macular degeneration (Petrukhin, 2007, Expert Opin Ther Targets). Therapeutic interventions targeting this complex include RBP4 antagonists like Tinlarebant (LBS-008) and Fenretinide, which aim to reduce serum RBP4 levels or disrupt the RBP4-STRA6 interaction to treat metabolic and degenerative ocular diseases (ClinicalTrials.gov NCT05244304).

Other names

STRA6-RBP4 complexRetinol-binding protein receptorVitamin A transport complexRBP4-STRA6 signaling complex

Antagonism of Retinol-binding protein 4 to prevent its interaction with the Stimulated by retinoic acid 6 receptor, thereby reducing retinol uptake and inhibiting downstream JAK/STAT signaling.