RBC membrane model depicting the structural proteins that, when abnormal, cause RBC membrane disorders. (A) Model of the RBC cytoskeleton quasihexagonal lattice forming a biconcave disc shape, supporting the lipid bilayer. An area of the cytoskeleton surface is shown “magnified” to demonstrate the arrangement of proteins within the hexagonal structure, focusing particularly on the proteins that, when defective, cause RBC membrane disorders. Illustration by Anastasios Manganaris (created using “blender” software, version 2.8). (B) α- and β-spectrin heterodimers associate head to head, as shown in the magnified circle, to form the spectrin tetramers that make the sides of each triangular unit in the hexagon. Each dimer head is composed of the N-terminal region of α-spectrin and the C-terminal region of β-spectrin. The junctional complex, at the corner of each triangle, is formed by an actin oligomer, with a length guided by tropomyosin, and capped by adducin and tropomodulin. Protein 4.1R enables the actin-spectrin association. The transmembrane protein complexes containing the integral membrane proteins band 3 and Rh-associated glycoprotein (RhAG) and the peripheral membrane proteins ankyrin and band 4.2 provide “vertical” linkages between the cytoskeleton and the lipid bilayer.