ZNF668 is a nucleolar zinc finger protein that functions primarily as a tumor suppressor through multiple mechanisms. As a transcriptional regulator, ZNF668 physically interacts with p53 and MDM2 to stabilize p53 and prevent its degradation, thereby suppressing breast cancer cell proliferation 1. In DNA damage response, ZNF668 acts as a key regulator of chr16 accessibility by promoting Tip60-mediated H2AX acetylation, facilitating recruitment of repair proteins to DNA lesions and enabling homologous recombination repair 2. ZNF668 suppresses cancer invasion and metastasis by downregulating Snail while upregulating epithelial markers E-cadherin and zonula occludens-1 3. Clinically, ZNF668 shows tumor suppressive properties across multiple cancer types: reduced expression in bladder cancer correlates with increased invasiveness 4, while in renal cell carcinoma, paradoxically, high ZNF668 expression predicts poor prognosis and associates with decreased immune infiltration 5. Biallelic ZNF668 mutations cause an autosomal recessive disorder (ZMAND) characterized by microcephaly, growth deficiency, severe developmental delay, brain malformation, and dysmorphic features, reflecting critical roles in neurodevelopment and DNA damage repair 6. ZNF668 promoter methylation varies among healthy individuals and may represent an epigenetic risk factor 7.