Irx2, belonging to the Iroquois homeobox gene family, is a transcription factor that plays significant roles in various biological processes. It has been associated with pathways like Wnt/β -catenin, PI3K/AKT, and is involved in regulating genes related to fibrosis, cell proliferation, invasion, and apoptosis. Its study using gene knockout models has been crucial in understanding its functions [1-10].

In male mice, CF-specific Irx2-knockout models showed that deletion of Irx2 in cardiac fibroblasts protected against angiotensin II-induced pathological fibrotic remodelling and improved cardiac function, indicating its role in promoting cardiac fibrosis [1]. In osteosarcoma, knockdown of Irx2 inhibited cell proliferation and invasion through the AKT/MMP9 signaling pathway [4]. In endometrial carcinoma, decreased expression of Irx2 facilitated cancer cell growth, and overexpression of Irx2 inhibited cell proliferation and invasion by transcriptionally repressing RUVBL1 [2]. Also, in hypertrophic cardiomyopathy, knockdown of Irx2 prevented mice from angiotensin II-induced ventricular dysfunction, cardiac hypertrophy, inflammation, and fibrosis, and JMJD2A was found to activate Irx2 transcription [3].

In conclusion, Irx2 is involved in multiple biological processes, especially in the context of diseases such as cardiac fibrosis, endometrial carcinoma, osteosarcoma, and hypertrophic cardiomyopathy. The use of Irx2 KO/CKO mouse models has been instrumental in revealing its roles in these disease conditions, providing insights into potential therapeutic targets.