HBG1 (hemoglobin subunit gamma 1) encodes the gamma globin chain, which combines with alpha chains to form fetal hemoglobin (HbF, α2γ2) 1. The gene functions in oxygen transport and binding within the hemoglobin complex, with expression normally occurring during fetal development but being silenced after birth through a developmental switch to adult hemoglobin 2. HBG1 silencing in adult erythroid cells involves multiple regulatory mechanisms. The transcription factors NFIA and NFIX repress HBG1/2 both directly and indirectly through BCL11A activation 3, while HIF1α binding to regulatory elements downstream of HBG1 and HBG2 regulates their expression during stress erythropoiesis 2. Additionally, CpG methylation at HBG1 promoters, maintained through UHRF1-mediated mechanisms, contributes to gene silencing 4. Clinically, HBG1 reactivation represents a therapeutic strategy for β-hemoglobinopathies including sickle cell disease and β-thalassemia. Multiple gene-editing approaches—including CRISPR-Cas9 enhancer disruption 1, adenine base editors 5, and transformer base editors 6—can reactivate HBG1 expression to therapeutic levels in patient hematopoietic stem cells. These strategies demonstrate durable HbF induction with minimal off-target effects, offering potentially curative alternatives to current pharmacotherapies 7.