The erythrocyte membrane skeleton composed of spectrin, actin, and several other proteins is essential for the maintenance of the erythrocyte shape, reversible deformability, and membrane structural integrity in addition to controlling the lateral mobility of integral membrane proteins. In this review, we shall give an historical development of the current model of the erythrocyte membrane skeleton. We will then describe how the experimental technology developed to study the normal membrane skeleton has paved the way for the recent identification of alterations of skeletal protein interactions in hereditary spherocytosis, hereditary elliptocytosis, and hereditary pyropoikilocytosis. We will conclude with a discussion of some of the more exciting and promising directions for future research that are currently being initiated in this vanguard field of cell biology.
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