Asxl2, an epigenetic regulator, is a transcription regulator and a research hotspot for tumor detection [1]. It belongs to the ETP family and interacts with PPARγ [3]. ASXL2 is involved in multiple biological processes and associated with various pathways, playing a crucial role in maintaining normal physiological functions. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its functions.

In KO mouse models, global deletion of Asxl2 prevents weight gain, and myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure [2]. Asxl2 -/- mice are insulin resistant, lipodystrophic, and severely osteopetrotic due to failed osteoclast differentiation [3]. In hematopoiesis, Asxl2 is essential for normal hematopoiesis. Its loss causes progressive hematopoietic defects, promotes myeloid expansion, and can lead to myeloid malignancies like myelodysplastic syndrome (MDS)-like disease or myeloid leukemia [4,5,6].

In conclusion, Asxl2 is a master regulator of skeletal, lipid, and glucose homeostasis, and is essential for normal hematopoiesis. The study of Asxl2 KO mouse models has provided insights into its role in obesity, metabolic diseases, and myeloid malignancies, contributing to our understanding of the underlying biological mechanisms and potential therapeutic targets in these disease areas.