ZNF280C (zinc finger protein 280C) is a C2H2 zinc finger-containing transcription factor with multifaceted roles in gene regulation and DNA damage response. As a DNA-binding transcription factor, ZNF280C occupies genomic intervals and coordinates with CTCF and cohesin binding to regulate chrX architecture 1. Mechanistically, ZNF280C maintains epigenetic repression at H3K27me3-marked loci, likely by recruiting the repressor SMCHD1 to counteract CTCF/cohesin activities and condense chrX at tumor suppressor gene cis-elements 1. Additionally, ZNF280C functions as a DNA damage response protein; it binds single-stranded DNA, localizes to double-strand breaks and stalled replication forks, and represses homologous recombination by inhibiting MRE11 binding and slowing DNA end resection 2. Clinically, ZNF280C exhibits significant disease relevance. In colorectal cancer, ZNF280C is highly expressed in primary tumors and metastases, where it promotes tumorigenesis and is required for Apc-driven intestinal carcinogenesis; its silencing inhibits proliferation, migration, and metastasis 1. Elevated ZNF280C levels independently predict worse prognosis in CRC patients 1. In attention-deficit/hyperactivity disorder, ZNF280C mRNA expression differentiates ADHD patients from controls and contributes to predictive models (AUROC=0.98) 3. Exercise training alters ZNF280C DNA methylation in skeletal muscle, suggesting metabolic regulation 4.