CXXC5 (CXXC finger protein 5) is a zinc-finger transcription factor that functions as a critical signal integrator and epigenetic regulator 1. It binds preferentially to unmethylated CpG islands in gene promoters, enabling its role as a DNA-binding transcription factor without intrinsic catalytic domains 1. CXXC5 coordinates multiple signaling pathways including Wnt/β-catenin, TGF-β, BMP, and ATM-p53 pathways, positioning it as a key regulator of cell proliferation, differentiation, and apoptosis 1. In hematopoietic stem cells, CXXC5 promotes self-renewal and suppresses differentiation; its knockout reduces proliferation while overexpression enhances it 2. CXXC5 negatively regulates Wnt/β-catenin signaling through interaction with Dishevelled, and disrupting this interaction stimulates hair regrowth and wound-induced hair follicle neogenesis 3. Pathologically, CXXC5 dysregulation is implicated in cancer development. In astroblastoma, MN1-CXXC5 fusion proteins drive oncogenic transformation of ventral telencephalon neural progenitors by activating PDGFRα and other shared transcriptional networks 4. In prostate cancer, CXXC5 upregulation at CpG-rich AR binding sites contributes to enzalutamide resistance 5. CXXC5 expression is regulated by glucocorticoids in the brain, linking it to stress response mechanisms 6. These findings establish CXXC5 as a pivotal therapeutic target across multiple disease contexts.