UHRF1 is a pivotal regulator of DNA methylation, and it engages in complex interactions with epigenetic modulators such as DNMT1, DNMT3A/B, HDAC1, and PRMT5 to facilitate DNA methylation maintenance and histone modifications that govern gene expression.[18, 29, 30] Therefore, we hypothesized that UHRF1 might bind to UMRs, thereby increasing DNA methylation levels and consequently activating NKX2‐5 and LHX1 transcription in ESCC cells. This evidence concerns the gene DNMT1 and esophageal squamous cell carcinoma.