In erythrocytes, Protein 4.1R is essential for membrane integrity. Deficiencies cause congenital hemolytic anemia. We have shown that there are many isoforms of P4.1R in other tissues. These participate in the mitotic apparatus, costameres, tight junctions, and adherens junctions. We are studying the structure function relationships of these isoforms. We also study the regulated pre-mRNA splicing events that govern their tissue and differentiation stage expression. We have identified a novel splicing factor induced during erythropoiesis that is critical to regulated P4.1R splicing and have characterized the mechanism by which it alters splicing.