The purpose of the proposed study is to investigate 3 newly discovered, unique defects in band 3, the major anion transport and acid-base balance protein. One of the defects represents a recognized autosomal recessive disease and is associated with ion and glucose transport abnormalities and a serious progressive neuropsychiatric disorder (familial amyotrophic chorea with acanthocytosis). Another disease presents biochemically and immunologically as accelerated aging of young and middle aged red blood cells. The reticulocyte count is -20%. The third disease is characterized by acanthocytosis and increase anion transport. It is called "high- molecular weight band 3" because there is an addition of several peptides in the anion transport region. Band 3 is a ubiquitous protein. Like the RBC proteins spectrin, ankyrin, 4.1, and actin, it is present in brain and all other cells examined. The specific aims of this project are to (1) determine what functional defects are associated with band 3 structural defects; (2) define the structural defects in terms of band 3 domains and amino acid sequence; (3) determine alterations in DNA sequence of the band 3 gene of affected individuals by sequencing regions of the gene which correspond to regions of the protein which appear altered in the peptide maps of the patient's band 3 proteins; (4) determine the mode of inheritance of band 3 defects in kindreds; (5) identify other defects in band 3 in the population.