AFP is a glycoprotein with a single glycosylation site at a specific argininne residue. Three glycosylation variants occur in serum reflecting different carbohydrate chains linked at this single position. These variants can be differentiated based on their relative binding to a lectin (carbohydrate binding protein) isolated from lentil seeds. This lectin, referred to as Lens culinaris agglutinin (LCA), binds to variants AFP-L1, AFP-L2, and AFP-L3 with increasing affinity. Serum AFP levels are markedly elevated in the neonate because AFP is synthesized in large quantities during embryonic development by the fetal yolk sac and by the fetal liver.

AFP-L1, which has the weakest binding to LCA, is the predominant fraction in patients with nonmalignant liver diseases, such as chronic hepatitis and liver cirrhosis.