ZNF638 is a zinc finger transcription factor with multiple regulatory roles across distinct biological processes. Structurally, it binds to cytidine clusters in double-stranded DNA 1 and localizes to nuclear bodies containing splicing factors 2. In viral defense, ZNF638 serves as a master epigenetic regulator that silences unintegrated retroviral DNA by recruiting the HUSH complex, SETDB1, and histone deacetylases HDAC1/HDAC4 to repress viral transcription 1. In metabolic regulation, ZNF638 controls hepatic de novo lipogenesis through interaction with USP7, which stabilizes ZNF638 and promotes SREBP1C cleavage via AKT/mTORC1 signaling, ultimately regulating lipogenic enzymes 3. During adipogenesis, ZNF638 acts as a transcriptional cofactor of CEBP proteins to induce PPARγ expression and participates in alternative splicing regulation of adipogenic genes 2. Clinically, ZNF638 variants associate with disease progression in multiple sclerosis, with rs10191329 linked to accelerated disability accrual and increased neurodegeneration 45. Additionally, ZNF638 contributes to open-angle glaucoma risk 6, and low ZNF638 expression predicts improved response to immune checkpoint inhibition in glioblastoma and melanoma by derepressing endogenous retroelements and activating antiviral immunity 7.