Receptor for retinol uptake STRA6 (STRA6)

STRA6 (Receptor for retinol uptake STRA6) is a multi-transmembrane cell-surface protein that functions both as a **receptor and transporter** for retinol (vitamin A) by mediating its uptake from plasma retinol binding protein (RBP) into cells[1][2][4][5]. Unlike typical transporters, STRA6 additionally acts as a cytokine-like receptor, activating the **JAK/STAT signaling pathway** upon RBP-ROH binding, which regulates gene transcription (notably SOCS3, a negative regulator of insulin signaling)[1][2]. STRA6’s activity is essential for retinol delivery especially to tissues behind blood/tissue barriers such as the eye, placenta, and brain[4]. Disruption of STRA6 can result in serious developmental defects and is linked by genetic association to metabolic diseases, including type 2 diabetes—making it a biologically and medically important therapeutic target[1][3]. Because it orchestrates both nutrient uptake and signal transduction, STRA6 is considered the prototype for a novel family of **cytokine signaling transporters**[1][2]. Key mechanistic features: - STRA6 binds extracellular RBP-retinol complex, transfers retinol into the cell, and hands it off to intracellular CRBP-I, coordinated with local retinol metabolism (e.g., LRAT activity)[1][2][3]. - Activation of STRA6’s signaling (JAK2/STAT5 phosphorylation) is dependent upon successful retinol transfer and likewise is required for efficient retinol uptake[1][2]. - Mutations in STRA6 can cause congenital eye defects (e.g., Matthew-Wood syndrome) or impair systemic vitamin A delivery[3][4]. No specific clinical drugs are currently approved for STRA6 modulation, but it is a subject of ongoing basic and translational research due to its dual function and disease links[1][2][3].

Other names

Stimulated by retinoic acid 6 protein homologSLC69A1Retinol-binding protein receptor STRA6RBP receptorRetinol binding protein 4 receptorPP14296MCOPCB8MCOPS9FLJ12541

Drugs would be expected to modulate retinol transport or block/recruit downstream JAK/STAT signaling. No clinically approved drugs for this mechanism[1][2].