holoRBP4

holoRBP4 is the retinol-bound form of retinol-binding protein 4 (RBP4), a secreted transport protein of the lipocalin family that shuttles vitamin A (retinol) through the bloodstream. The RBP4 protein is primarily produced by the liver and circulates in plasma, delivering retinol to peripheral tissues such as the retina, adipose tissue, and immune cells.

In circulation, holoRBP4 often associates with transthyretin (TTR) to form a larger complex that reduces filtration by the kidneys and prolongs retinol circulation. Retinol is transferred to cells via the cell-surface receptor STRA6 (stimulated by retinoic acid 6), which mediates uptake of retinol from holoRBP4 into the cytoplasm where it can be metabolized or stored. The carrier can exist in the apo form, lacking bound retinol, which can be reloaded in hepatic or extrahepatic tissues.

Physiological roles: holoRBP4 maintains vitamin A homeostasis and supplies retinol to tissues with high demand. Because retinol status reflects dietary intake and metabolism, holoRBP4 levels can serve as an indirect indicator of vitamin A status in some settings; however, measurement of serum RBP4 alone does not always reflect tissue retinol stores.

Clinical relevance: Altered RBP4 and holoRBP4 levels have been investigated in metabolic disorders, and some studies link RBP4 to insulin resistance and obesity, though findings are inconsistent. Rare genetic variants of RBP4 can disrupt retinol transport and cause vitamin A–related phenotypes. Ongoing research seeks to clarify holoRBP4’s utility as a biomarker and its role in retinoid signaling.