Sickle cell anemia was the first molecular disease discovered in the world in 1949, thus ushering in the era of molecular biology of diseases. Its molecular pathology is a single base mutation in the gene. The sixth codon of the normal gene is GAG, which translates to glutamic acid. After mutation, it becomes GTG, which translates to valine. This single amino acid substitution forms HbS. Clinically, there are three main forms of hemoglobin S disease: ① homozygous state, i.e. sickle cell anemia; ② heterozygous state, i.e. sickle cell trait; ③ double heterozygous state of hemoglobin S and other abnormal hemoglobins, including hemoglobin S thalassemia, hemoglobin C disease, hemoglobin D disease, etc. In the deoxygenated state, the solubility of HbS is 1/40 of that of deoxygenated HbA. Therefore, deoxygenation can make red blood cells stiff and deformed, becoming sickle-shaped, hence the name.