CXXC5, a member of the CXXC-type zinc-finger protein family, plays a pivotal role in epigenetic regulation. It binds to unmethylated CpG islands in gene promoters via its CXXC domain, acting as a transcription factor and epigenetic factor without a catalytic domain. CXXC5 is an important signal integrator, regulated by multiple signaling pathways and capable of regulating TGF-β, Wnt, ATM-p53 and other pathways, crucial for embryonic development and adult tissue homeostasis [1].

CXXC5 knockout (KO) mouse models have revealed its diverse functions. In hair-related studies, Cxxc5 KO mice displayed accelerated hair regrowth, indicating CXXC5 is a negative regulator of the Wnt/β-catenin pathway in hair regrowth [2]. In metabolic disease research, Cxxc5-/-mice fed a high-fat diet were resistant to metabolic dysregulation, suggesting that CXXC5 overexpression in visceral adipose tissues may contribute to obesity-related diabetes [3].

In conclusion, CXXC5 is essential for multiple biological processes, regulating cell proliferation, differentiation, and apoptosis. Model-based research, especially KO mouse models, has shown its significance in diseases such as tumorigenesis, hair loss, and obesity-related metabolic diseases. Understanding CXXC5 provides insights into disease mechanisms and potential therapeutic targets.