Hbs1l, encoding HBS1-like translational GTPase, is a critical component of the cell's translational quality control pathways. It is crucial for ribosomal rescue, and its function is conserved across species [2,3,7]. In the context of erythroid development, the HBS1L-MYB intergenic region has been associated with elevated fetal hemoglobin (HbF) levels, which can alleviate anemia in conditions like thalassemia and sickle cell disease [1,4,5,6,8].

In mammalian studies, Hbs1l-deficient mouse models (Hbs1ltm1a/tm1a) show congenital anomalies, developmental delay, and retinal dystrophy. Loss of Hbs1l leads to abnormal 80S monosome accumulation, depletion of Pelota protein, and proteomic alterations in the retina, with down-regulation of proteins involved in phototransduction, cilium assembly, and photoreceptor cell development [2,3,7]. In β0-thalassemia/HbE erythroid cells, knockdown of Hbs1L using shRNA triggers an up-regulation of γ-globin mRNA and an increase in the percentage of fetal hemoglobin, with modest effects on cell differentiation [6].

In conclusion, Hbs1l is essential for ribosomal rescue and plays a significant role in translational quality control. Its deficiency in mouse models recapitulates human phenotypes such as developmental delay and retinal dystrophy. In the context of blood disorders, Hbs1l and its intergenic region with MYB are promising targets for modulating HbF levels, offering potential therapeutic strategies for β-hemoglobinopathies.