Ilf3, also known as Interleukin enhancer-binding factor 3, is a double-stranded RNA-binding protein generated by alternative splicing of the Ilf3 gene [5]. It is involved in multiple cellular processes such as RNA metabolism, regulation of the cell cycle, and enzymatic activities. Ilf3 participates in pathways like mTORC1-dependent amino acid sensing, Keap1-Nrf2 signaling, and is associated with diseases including abdominal aortic aneurysm, multiple myeloma, and colorectal cancer [2,3,4]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In male mice, macrophage-specific Ilf3 deficiency attenuates abdominal aortic aneurysm progression, while its elevation exacerbates the lesions. Mechanistically, macrophagic Ilf3 increases NF-κB activity by accelerating p105 mRNA decay and represses anti-inflammatory action by inhibiting the Keap1-Nrf2 signaling pathway [1]. In atherosclerotic calcification, smooth muscle-conditional and macrophage-conditional Ilf3 knockout and transgenic mice studies showed that hyperlipidemia increases Ilf3 expression, which promotes calcification by mediating BMP2 and STAT1 transcription [6].

In conclusion, Ilf3 is crucial in regulating inflammation, amino acid sensing, and metabolic reprogramming, as revealed through model-based research. The use of Ilf3 KO/CKO mouse models has significantly contributed to understanding its roles in abdominal aortic aneurysm and atherosclerotic calcification, providing potential therapeutic targets for these diseases.