retinolbinding

Retinol-binding refers to the interaction of retinol (vitamin A alcohol) with specific proteins that solubilize, transport, and regulate its availability to tissues. The term encompasses both intracellular carriers, such as cellular retinol-binding proteins CRBP1 and CRBP2, and the circulating retinol-binding protein RBP4 that escorts retinol in the bloodstream. In circulation, RBP4 often forms a complex with transthyretin (TTR), which helps prevent the retinol–RBP4 complex from being filtered out by the kidneys.

Retinol transport and uptake are organized through a coordinated system. In the liver, retinol is stored as retinyl esters and mobilized when needed. Circulating retinol binds to RBP4 to form the holo-RBP4 complex, which carries retinol to peripheral tissues. The cell-surface receptor STRA6 binds the holo-RBP4-retinol complex and mediates retinol uptake into cells. Once inside the cell, CRBP1, CRBP2, and related proteins bind retinol or retinaldehyde, guiding its metabolism toward generation of retinoic acid or storage as retinyl esters.

Biological significance and clinical relevance are tied to essential roles in vision, immune function, epithelial integrity, and development. Proper retinol binding ensures vitamin A homeostasis and tissue supply. Disruptions in transport, due to liver disease, malnutrition, or genetic mutations in RBP4, STRA6, or CRBP family members, can reduce bioavailable retinol or impair uptake. Abnormally high circulating RBP4 levels have been linked in some studies to metabolic conditions such as insulin resistance, while low levels reflect deficiency. Retinol binding remains a central concept in nutritional biochemistry and vitamin A physiology, with ongoing research into its therapeutic implications.