Asb2, the ankyrin repeat and SOCS box containing 2 gene, forms an E3 ubiquitin ligase complex. It is involved in multiple biological pathways, including the ubiquitin-proteasome system, which is crucial for the selective degradation of proteins. This gene plays an important role in processes like cardiogenesis, hematopoiesis, and immune cell function, and is associated with diseases such as lymphoma and congenital heart disease [1,2,3,5]. Genetic models, especially KO and CKO mouse models, have been valuable in studying Asb2's functions.

In cardiogenesis, Asb2 acts as the E3 ligase of SMAD9, regulating BMP signalling. Knockdown of Asb2 in zebrafish led to a thinned ventricular wall and dilated ventricle, phenotypes rescued by simultaneous Smad9 knockdown [1]. In mice, conditional deletion of Asb2 using Nkx+/Cre.Asb2fl/fl and AHF-Cre.Asb2fl/fl led to embryonic lethality, incomplete heart looping, and double outlet right ventricle (DORV). These defects were related to up-regulation of its target Filamin A (Flna), and concurrent Flna deletion partially rescued the lethality [3].

In NK cells, Asb2 is regulated by AHR, and its knockdown inhibited cell migration. Activation of AHR induced ASB2-dependent filamin A degradation, and reduction of filamin A increased NK cell migration [4]. In leukemia cells, ASB2 targets filamins A and B for proteasomal degradation, and its knockdown delays retinoic acid-induced differentiation [5].

In conclusion, Asb2 is essential for normal development and function in various biological systems. The study of Asb2 KO and CKO mouse models has provided insights into its role in cardiogenesis, immune cell function, and hematopoiesis, with implications for understanding congenital heart disease and leukemia.