Foxj3, a member of the Forkhead box gene family, is involved in multiple biological functions and pathways. It is an important regulator in processes such as fat thermogenesis, cell proliferation, mitochondrial homeostasis, and muscle fiber type determination [1,2,3,5]. Genetic models, especially KO/CKO mouse models, have been crucial in elucidating its functions.

In fat tissue, adipose-specific Foxj3 knockout impairs the thermogenic function of brown fat, leading to morphological whitening, obesity, increased fasting blood glucose levels, and hepatic steatosis. It also inhibits the browning of inguinal white adipose tissue. Conversely, Foxj3 overexpression enhances the thermogenic program and improves systemic metabolism [1]. In breast cancer cells, modulating Foxj3 expression affects cell proliferation, migration, and invasion, and it modulates the expression of Snail, a transcription factor involved in epithelial-mesenchymal transition [2]. In neuroblastoma, higher FOXJ3 expression is associated with lower risk, and its overexpression reduces cell density, proliferation, and migration [4]. In spermatogenesis, conditional knockout of Foxj3 from spermatogonia or meiotic spermatocytes leads to male sterility, with different etiologies: loss of spermatogonia or meiotic arrest [6].

In conclusion, Foxj3 plays essential roles in fat thermogenesis, cancer-related cell behaviors, spermatogenesis, and muscle-related processes. The KO/CKO mouse models have significantly contributed to understanding its functions in obesity, metabolic diseases, breast cancer, and neuroblastoma, providing potential therapeutic targets for these diseases.