ZNF326 (zinc finger protein 326) is a transcription factor that plays diverse roles in cellular regulation and disease pathogenesis. As a core component of the DBIRD complex, ZNF326 integrates transcript elongation with alternative splicing regulation, particularly affecting exons in (A+T)-rich DNA regions [UniProt]. The protein demonstrates tissue-specific transcriptional activity, directly binding to gene promoters through its C2H2 zinc finger structure to regulate expression of target genes including ERCC1 and HDAC7 1 2. ZNF326 exhibits complex roles in cancer biology, functioning as both a tumor suppressor and oncogenic factor depending on context. In triple-negative breast cancer, it acts as a tumor suppressor, regulating epithelial-mesenchymal transition and cancer stem cell pathway genes 3. However, in colorectal cancer, ZNF326 promotes tumor progression by activating TGF-β/SMAD signaling through ADP-ribosylation-mediated stabilization 4 and enhancing EMT 5. The protein also facilitates immune evasion by promoting PD-L1/PD-1 interactions 4. Clinically, ZNF326 shows promise as both a therapeutic target and biomarker. Its expression correlates with tumor grade in glioma 2 and treatment response in depression, where genetic variants associate with antidepressant efficacy 6. Additionally, ZNF326 mediates innate immune responses during DNA replication stress through PRMT5-dependent modification 7.