The erythrocyte band 3 protein (AE1, anion exchanger 1) performs two critical functions: chloride-bicarbonate exchange (for CO₂ transport) and structural anchoring of the spectrin-actin cytoskeleton. Hereditary spherocytosis most commonly involves mutations affecting which component of the vertical linkage between band 3 and spectrin?

• A Protein 4.1 — links actin-spectrin junctions to glycophorin C
• B Ankyrin — links band 3 (and band 4.2) to beta-spectrin ✓
• C Adducin — caps the barbed ends of actin filaments in the junctional complex
• D Dematin — bundles actin filaments at the junctional complex

Explanation

Hereditary spherocytosis (HS) is most commonly caused by mutations in ankyrin (ANK1, ~50% of cases), which forms the central 'vertical' link between the cytoplasmic tail of band 3 and beta-spectrin. Deficiency of ankyrin destabilizes spectrin membrane binding, causing areas of lipid bilayer to detach as vesicles (lipid microvesiculation), progressively reducing surface area and converting the cell to a sphere. Spherocytes are less deformable and are trapped and hemolyzed in the splenic red pulp. Protein 4.1 mutations cause hereditary elliptocytosis (disrupting the horizontal spectrin-actin-4.1 junctional complex).

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.