UHRF1 is an E3 ubiquitin-protein ligase that serves as a key epigenetic regulator by bridging DNA methylation and chr19 modifications 1. Its primary function involves maintaining DNA methylation patterns during replication by recognizing hemimethylated CpG sites and recruiting DNMT1 through histone H3 lysine-18 ubiquitination (H3K18ub) 12. UHRF1 acts as both a histone reader and writer, specifically binding H3K9me3 marks and catalyzing H3K18ub modification, which creates a docking site for DNMT1 1. Beyond DNA methylation maintenance, UHRF1 promotes crosstalk between histone modifications by enhancing SUV39H1/H2 methyltransferase activity, leading to H3K9me3 accumulation and heterochromatin reinforcement 1. Disease relevance includes significant roles in cancer progression, where UHRF1 maintains oncogenic DNA hypermethylation and silences tumor suppressor genes 3. Additionally, cytoplasmic UHRF1 promotes MHC-I degradation, contributing to immune evasion 4, while its upregulation drives ferroptosis in pulmonary fibrosis by epigenetically repressing GPX4 and FSP1 5. Clinically, UHRF1 expression correlates with poor cancer prognosis and represents a potential therapeutic target, as disrupting its chr19 reader activities can reactivate silenced genes and enhance immunotherapy efficacy 34.