In hereditary spherocytosis, the most common molecular defect responsible for loss of membrane stability involves which protein?

• A Protein 4.2, directly anchoring lipid bilayer
• B Glycophorin A, forming the MN blood group antigen
• C Ankyrin-1 (ANK1), linking spectrin to band 3 ✓
• D Stomatin, regulating membrane channel conductance

Explanation

Ankyrin-1 deficiency is the most common molecular defect in hereditary spherocytosis (HS), accounting for approximately 50% of dominant and 75% of recessive cases. Ankyrin links the beta-spectrin of the horizontal cytoskeleton to the transmembrane protein band 3 (anion exchanger 1); its deficiency weakens this vertical interaction, causing membrane lipid loss, surface area reduction, and spherocyte formation. Mutations in alpha- and beta-spectrin, band 3, and protein 4.2 account for the remaining HS cases.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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