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Alpha globin chains are polypeptide subunits of hemoglobin, the oxygen‑transport protein in red blood cells. Two alpha chains associate with two beta, delta, or gamma chains to form the four‑subunit tetrameric hemoglobin (HbA, HbF, HbA2). They are encoded by the HBA1 and HBA2 genes on chromosome 16, each gene producing a transcript that is translated into a 141‑residue protein. The N‑terminal methionine is cleaved during maturation, yielding a mature chain of 140 residues.

Alpha globin contains a single α‑helix bundle that binds a heme group. The proximal histidine (His87 in the mature chain) coordinates the iron ion, while the distal histidine modulates ligand binding. The alpha chain contributes to the tetramer's quaternary structure, influencing oxygen affinity and cooperativity. The normal adult hemoglobin (HbA) has two alpha and two beta chains, but fetal hemoglobin (HbF) is composed of two alpha and two gamma chains.

Mutations in HBA1 or HBA2 cause alpha‑thalassemia, characterized by insufficient production of alpha chains. Overproduction leads to alpha‑thalassemia intermedia or hemoglobin H disease. Genetic deletions or point mutations reduce chain synthesis, causing imbalance that results in ineffective erythropoiesis, hemolytic anemia, and clinical variability from asymptomatic to severe, life‑threatening disease. Treatment options include blood transfusion, splenectomy, iron chelation, and investigational gene‑therapy approaches.

In addition to genetic disorders, alpha globin plays a role in erythrocyte development, modulation of reactive oxygen species, and interaction with membrane proteins. Research also investigates alpha chain variants as biomarkers for cardiovascular disease risk and as targets for therapeutic modulation of hemoglobin oxygen affinity.