Deficiency of which membrane protein leads to hereditary spherocytosis?

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Defects in the red cell membrane skeleton disrupt the tethering of the lipid bilayer to the cytoskeleton, causing the membrane to lose surface area and form spherocytes. Spectrin is the primary cytoskeletal lattice beneath the membrane; it provides the structural framework that maintains the biconcave shape. When spectrin is deficient, the cytoskeletal network weakens, the membrane becomes unstable, and vesiculation during circulation reduces surface area relative to volume. The resulting sphere-like, less deformable cells are trapped and destroyed in the spleen, producing hereditary spherocytosis. While other proteins (like ankyrin or band 3) can also be involved, spectrin deficiency directly undermines the main structural scaffold, making it the classic cause.