Erythrocytes are naturally a biconcave disc, which results in a larger membrane surface to volume ratio than a sphere-shaped disc. These cells have the strength and flexibility to survive 120 days in circulation. Their peripheral proteins stabilize the membrane and are responsible for their shape. These proteins include sprecrin, actin, ankryn, and band protein 4. Peripheral proteins are attached to the red blood cell (RBC) membrane. Ankyrin-1 stabilizes the membrane by linking beta-spectrin to band-3. Band 3 protein is part of the integral membrane and functions as an anion exchanger, glucose transporter, and water channel (Hamasaki, 1999). A genetic disorder weakening the vertical bond between the peripheral protein membrane and the integral protein membrane can cause reduction in membrane surface area, reduction in surface area-to-volume ratio, and formation of spherocytes, sphere-shaped red blood cells. An example of this would be a weakened link between band 3 protein and ankryin-1 (Perrotta, Gallagher, & Mohandas, 2008). This is the result of heterogeneous alterations in the genes encoding proteins responsible for binding the red blood cell's inner membrane backbone to its outer lipid bilayer. An inherited red blood cell abnormality caused by defects in membrane proteins is known as hereditary spherocytosis (HS). The most common cause of HS is mutation of the gene encoding the membrane protein ankyrin-1 (Gallagher, Steiner, Liem, Owen, Cline, Seidel, Garrett, & Bodine, 2010). Hereditary spherocytosis is the most common form of hereditary hemolytic. anemia in the United States, Northern Europe, and notably Japan, affecting one person in 2000. HS can be found in most racial groups, but it is less common in African American and South Asian ...... middle of paper .. .... 1999). The role of band 3 protein in oxygen delivery by red blood cells. Indian Journal of Clinical Biochemistry, 14(1), 49-58. Retrieved February 23, 2014 from http://www.ncbi.nlm.nih.gov/pmc/articles/PM3453557/Garg, P., Kumar, A., Tecckchandani, N., Hadke, N., (2008). ). Hereditary spherocytosis coexisting with Gilbert syndrome: a diagnostic dilemma. Singapore Med J. Retrieved February 22, 2014 from http://smj.sma.org.sg/4911/4911cr5.pdfPerrotta, S., Gallagher, P., Mohandas, N., (October 2008). Hereditary spherocytosis. The Lancet, Vol. 372, p. 1411-1426. Accessed February 22, 2014, from http://www.medicine.wisc.edu/~williams/spherocytosis_lancet_2008.pdf Zhi, ZW (September 2013). Clinical research on modified laparoscopic splenectomy in the treatment of children with hematologic diseases. Accessed February 22, 2014 from http://omim.org/entry/182900