HIVEP2 is a zinc finger transcription factor that binds the DNA sequence 5'-GGGACTTTCC-3' found in viral and cellular gene enhancers, including those regulating immune responses and interferon signaling. It functions as an NF-κB inhibitor regulating inflammatory gene expression 1. Mechanistically, HIVEP2 acts as a transcriptional regulator controlling multiple gene networks. In regulatory T cells, HIVEP2 coregulates gene networks with SATB1 and is essential for T cell-mediated immunosuppression 2. In glioblastoma, YTHDF2-mediated m6A-dependent mRNA decay of HIVEP2 downregulates its expression, promoting tumorigenesis and cholesterol dysregulation 3. HIVEP2 expression decreases in glioma with increasing malignancy grade, and its overexpression inhibits glioma cell growth and induces differentiation 4. HIVEP2 pathogenic variants cause autosomal dominant intellectual developmental disorder with multisystem features. Individuals with HIVEP2-related disorder exhibit developmental delay, hypotonia, language impairment, gastroesophageal reflux, and significant impairments in adaptive and social behaviors 56. In schizophrenia, HIVEP2 downregulation in neurons is associated with neuroinflammation and increased pro-inflammatory gene expression 1. Clinically, HIVEP2 represents a therapeutic target for both oncology (glioblastoma) and immunotherapy applications, though single-gene knockout alone appears insufficient for certain cellular protection strategies 7.