BackgroundA potential strategy for treatment of sickle cell disease (SCD) and β-thalassemia in adults is reactivation of the ε- and γ-globin genes in the adult. We aimed to identify trans-activators of ε- and γ-globin expression and provide new candidate targets for effective treatment of sickle cell disease (SCD) and β-thalassemia through activation of ε- and γ-globin genes in adults.ResultsWe identified a CTD small phosphatase like 2 (CTDSPL2) gene that had higher transcription levels in umbilical cord blood (UCB) than in adult bone marrow (BM). Also, transcription of the CTDSPL2 gene increased significantly during erythroid differentiation. Further, we found that overexpression of CTDSPL2 could obviously improve the expression of ε- and γ-globin genes in K562 cells. Meanwhile, the repression of CTDSPL2 by RNA interference decreased expression of ε- and γ-globin genes but did not inhibit the increase of globin gene expression during K562 erythroid differentiation. In addition, the enforced expression of CTDSPL2 gene mediated by lentiviruses could also increase ε- and γ-globin gene expression during erythroid differentiation of CD34+ cells derived from UCB.ConclusionCTDSPL2 gene can obviously improve the expression of ε- and γ-globin genes in K562 cells and CD34+ cells derived from UCB. Our study provides a new candidate target for effective treatment of SCD and β-thalassemia.