EKLF regulates globin switching. During embryonic and fetal development or in EKLF-haploinsufficient adults (left), EKLF levels are relatively low, resulting in low levels of adult β-globin and Bcl11a and high levels of γ-globin. In adults with 2 functional copies of EKLF (right), increased expression of EKLF in definitive red blood cells promotes high levels of adult β-globin and Bcl11a expression, the latter of which in turn represses γ-globin expression. (Modified from Bieker.⁹⁴ )