Irx5, the Iroquois homeobox transcription factor 5, plays significant roles in multiple biological processes. It is involved in pathways related to cell differentiation, energy homeostasis, and DNA damage repair. Genetic models, especially KO mouse models, have been crucial in elucidating its functions, highlighting its importance in understanding various physiological and disease-related mechanisms [1-10].

In adipose-related studies, Irx5-KO mice were leaner and resistant to diet-induced obesity. Irx5 promotes adipogenesis of human bone marrow-derived mesenchymal stem cells (hMSCs) by repressing glycolysis and transcriptionally activating peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) [1,5,6].

In the context of hair follicles, Irx5-/-mice have delayed anagen onset, increased DNA damage, and diminished hair follicle stem cell (HFSC) proliferation, indicating its role in HFSC activation and DNA damage repair [2].

In the heart, Irx5-KO mice exhibited decreased global LV contractility associated with elevated fast transient outward K+ current (Ito,f) in endomyocardial cardiomyocytes, suggesting its role in establishing transmural contractile heterogeneities [4].

In colorectal cancer, IRX5-overexpressing cells had enhanced migration and invasion, and IRX5 promoted metastasis by negatively regulating the core components of the RHOA pathway, while in CRC cell lines, upregulation of IRX5 led to G1/S arrest and increased DNA damage-related markers [3,7].

In conclusion, Irx5 is essential in processes such as adipogenesis, DNA damage repair, cardiac contractility, and cancer development. The use of Irx5 KO mouse models has significantly contributed to understanding its role in obesity, hair follicle stem cell function, heart contractility, and colorectal cancer, providing insights into potential therapeutic targets for these disease areas.