Zinc alpha 2 glycoprotein (ZAG): A potential novel pharmacological target in diabetic retinopathy

Zinc alpha 2 glycoprotein (ZAG) is a 41 KDa secretory soluble glycoprotein found in different body fluids like the serum, saliva, sweat, breast milk, and urine. It is also found in tissues like the testis, epididymis, kidney, spleen, liver, lungs, heart, and brain. ZAG is an adipokine with multiple roles, including lipid mobilization, modulating glucose metabolisms, improving insulin sensitivity, inhibiting tumor proliferation through RNAse activity, and suppressing inflammation. Low levels of zinc and ZAG are linked to metabolic syndrome and are also reported as potential biomarkers for diabetic nephropathy. Interestingly zinc has been found to regulate the binding of ZAG to fatty acids. Based on very few reports on the vitreous ZAG and based on its known functions, we speculate that ZAG has a potential role in diabetic retinopathy. In this article, we discuss the structural component of the protein, its secretion from various tissues, and its distribution in multiple tissues in normal and disease conditions, especially in diabetes and its complications.