Arhgef2, also known as Rho/Rac guanine nucleotide exchange factor 2, is a key regulator that activates RhoA GTPase, thereby modulating cytoskeleton dynamics, cell division, and cell migration [5,6,7]. It is involved in multiple biological pathways, such as the RhoA/ROCK/MLC pathway crucial for cell migration [7]. Arhgef2 is of great biological importance in processes like neural differentiation, hematopoiesis, and tumorigenesis [3,5,7]. Genetic models, especially knockout mouse models, have been valuable in studying its functions.

In animal models, Arhgef2 deficiency leads to impaired neurogenesis, neurite outgrowth, and synaptic formation in the cerebral cortex by regulating m6A methylation of Npdc1 and Cend1 [3]. In hematopoietic stem cells, Arhgef2 knockout results in impaired hematopoietic recovery and a production deficit, along with an increased frequency of misoriented divisions [5]. In colorectal cancer, YTHDF1 promotes ARHGEF2 translation, and ARHGEF2 siRNA encapsulated by lipid nanoparticles significantly suppresses tumor growth and metastasis in vivo [1]. In prostate cancer, androgen deprivation restores ARHGEF2 to promote neuroendocrine differentiation [2]. In hepatocellular carcinoma, ARHGEF2 overexpression is linked to malignant development, and it contributes to ER stress-related treatment resistance [4].

In summary, Arhgef2 is essential for neural differentiation, hematopoiesis, and normal cellular functions. Its dysregulation is associated with various diseases, including neurodevelopmental disorders, hematopoietic failures, and multiple types of cancers. Gene knockout mouse models have provided significant insights into Arhgef2's role in these disease areas, facilitating a better understanding of the underlying molecular mechanisms and potentially guiding the development of targeted therapies.