UHRF2 is an E3 ubiquitin ligase that plays multifaceted roles in epigenetic regulation, DNA repair, and cell cycle control. As a specific reader of 5-hydroxymethylcytosine (5hmC), UHRF2 recruits substrates to epigenetically modified sites for ubiquitination, thereby maintaining DNA methylation patterns and regulating gene expression 1. In cell cycle regulation, UHRF2 ubiquitinates cyclins CCND1 and CCNE1 to induce G1 arrest, and cooperates with UHRF1 as an interstrand crosslink sensor to recruit and activate FANCD2 for DNA repair 2. UHRF2 stabilizes the acetyltransferase TIP60 to regulate histone acetylation marks H3K9ac and H3K14ac, mechanisms disrupted in cancer cells 2. Clinically, UHRF2 expression inversely correlates with cancer progression. Loss of UHRF2 expression, often due to promoter hypermethylation, associates with reduced 5hmC levels and increased proliferative activity across multiple cancer types 1. In hepatocellular carcinoma and intrahepatic cholangiocarcinoma, UHRF2 overexpression promotes malignancy through PARP1-mediated autophagy and correlates with poor prognosis, microvascular invasion, and lymphatic metastasis 34. Conversely, UHRF2 deletion impairs hematopoietic stem cell function without inducing hematologic malignancy 5. In esophageal cancer, miR-196a suppresses UHRF2 expression to promote proliferation via the UHRF2/TET2 axis 6. These findings establish UHRF2 as both a critical epigenetic regulator and a context-dependent cancer biomarker.