most of exon 3 encode the N-terminal extracellular domain while the remainder of exon 3 and exon 4 encode transmembrane and cytoplasmic domains. Two isoforms are known and the gene is expressed in a wide variety of tissues including kidney, thymus, stomach, breast, adult liver and erythrocyte. In the non erythroid cell lines, expression is lower than in the erythrocyte and the protein is differentially glycosylated. In the erythrocyte glycophorin C makes up ~4% of the membrane sialoglycoproteins. The average number of O linked chains is 12 per molecule. The gene is expressed early in the development of the erythrocyte, specifically in the erythroid burst-forming unit and erythroid colony-forming unit. The mRNA from human erythroblasts is ~1.4 kilobases long and the transcription start site in erythroid cells has been mapped to 1050 base pairs 5' of the start codon. It is expressed early in development and before the Kell antigens, Rhesus-associated glycoprotein, glycophorin A, band 3, the Rhesus antigen and glycophorin B. In melanocytic cells Glycophorin C gene expression may be regulated by MITF. GPC appears to be synthesized in excess in the erythrocyte and that the membrane content is regulated by band 4.1 (protein 4.1). Additional data on the regulation of glycophorin C is here. In a study of this gene among the Hominoidea two finding unique to humans emerged: (1) an excess of non-synonymous divergence among species that appears to be caused solely by accelerated evolution and (2) the ability of the single GYPC gene to encode both the GPC and GPD proteins. The cause for this is not known but it was suggested that these findings might be the result of infection by Plasmodium falciparum. Molecular biology After separation of red cell membranes by SDS-polyacrylamide gel electrophoresis and staining with periodic acid-Schiff staining (PAS) four glycophorins have been identified. These have been named glycophorin A, B, C and D in order of the quantity present in the membrane – glycophorin A being the most and glycophorin D the least common. A fifth (glycophorin E) has been identified within the human genome but cannot easily be detected on routine gel staining. In total the glycophorins constitute ~2% of the total erythrocyte membrane protein mass. Confusingly these proteins are also known under different nomenclatures but they are probably best known as the glycophorins. Glycophorin C was first isolated in 1978. Glycophorin C and D are minor sialoglycoproteins contributing to