RBP4 gene

The RBP4 gene (RBP4 stands for retinol-binding protein 4) is a protein-coding gene located on chromosome 10q23.33. The signaling pathways associated with this gene include visual phototransduction and diseases of the neuronal system.

The encoded RBP4 protein (Retinol Binding Protein 4) belongs to the lipocalin family and is classified as an adipocytokine. The RBP4 protein is the specific carrier for retinol (vitamin A alcohol) in the blood (Peterson PA 1971). It transports retinol from the liver depots to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, which prevents its loss by filtration through the renal glomeruli. Transfers the bound all-trans-retinol to STRA6, which then facilitates retinol transport across the cell membrane (Berry DC et al. 2012).

As an active endocrine organ, adipose tissue secretes many adipokines and cytokines. These biomolecules, known as adipocytokines, play an important role in regulating energy homeostasis and metabolism throughout the body by influencing and altering the function of target tissues. Retinol-binding protein 4 (RBP4) has been linked to systemic insulin resistance, dyslipidemia, type 2 diabetes and other metabolic diseases (Nono Nankam PA et al. 2021). Vitamin A deficiency blocks the secretion of the binding protein post-translationally and leads to impaired delivery to epidermal cells.

There is ample evidence that both retinoids and retinol-binding protein 4 (RBP4) contribute to the development of liver disease. Since adipocyte-specific hRBP4 mice exhibit increased expression of tumor necrosis factor-α and leptin as well as "crown-like structures" in adipose tissue, it is hypothesized that adipose tissue undergoes RBP4-induced inflammation that stimulates increased lipolysis in adipocytes (Lee SA et al. 2016)

Diseases associated with RBP4 include microphthalmia/coloboma 10 and retinal dystrophy, iris coloboma and comedogenic acne syndrome.

1. Berry DC et al. (2012) Cross talk between signaling and vitamin A transport by the retinol-binding protein receptor STRA6. Mol Cell Biol 32:3164-3175.
2. Lee SA et al. (2016) Adipocyte-specific overexpression of retinol-binding protein 4 causes hepatic steatosis in mice. Hepatology 64:1534-1546.
3. Nono Nankam PA et al. (2021) Retinol-binding protein 4 in obesity and metabolic dysfunctions. Mol Cell Endocrinol 531:111312.
4. Peterson PA (1971). Studies on the interaction between prealbumin, retinol-binding protein, and vitamin A. J Biol Chem 246:44-49.
5. Romeo S et al. (2016) Regulation of retinol-binding protein 4 and retinol metabolism in fatty liver disease. Hepatology 64:1414-1416.