Akirin2 is an evolutionarily conserved nuclear protein. It has diverse essential functions, such as controlling the nuclear import of proteasomes, which is crucial for nuclear protein degradation [1]. It also acts as a key link between nuclear factor-κB and chromatin remodelers like the SWI/SNF complex, playing a role in transcriptional regulation in macrophages and B cells [2]. Akirin2 is involved in pathways related to embryonic development, innate immunity, angiogenesis, and cell proliferation and differentiation, making it biologically important. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In mice, constitutive knockout of Akirin2 is early embryonic lethal [5]. Cortex-restricted Akirin2 knockouts lead to extreme microcephaly, massive cell death of early cortical progenitors, and failure of normal proliferation and neuron production, indicating its essential role in early cortical development [5]. In neurons, restricting Akirin2 loss to excitatory cortical neurons results in progressive neurodegeneration via necroptosis, and reduction of Trp53 can rescue this, suggesting p53 pathways mediate Akirin2 functions [4]. In cancer research, in cholangiocarcinoma, silencing or overexpressing Akirin2 significantly affects cell proliferation, migration, invasion, and angiogenesis, and it is negatively regulated by miR-490-3p [3]. In gastric adenocarcinoma, high-expression of Akirin2 is associated with a poor survival rate, and it can be used as a biomarker for prognosis and guide chemotherapy and immunotherapy [6].

In conclusion, Akirin2 is essential for multiple biological processes including embryonic development, neuronal maintenance, and immune responses. Studies using KO/CKO mouse models have revealed its roles in neurodegenerative diseases and cancer, providing insights into disease mechanisms and potential therapeutic targets.