Single nucleotide polymorphism (SNPs) in several genetic modulators and cis-regulatory elements involved in the regulation of human HbF, i.e. HBG2, B cell CLL/lymphoma 11A (BCL11A), Kruppel-like factor 1 (KLF1) and MYB, can delay fetal-to-adult hemoglobin (Hb) switch, ameliorating the severity of β-thalassemia and sickle cell disease [9–20]. Here, KLF1 is linked to sickle cell disease.