Here, we identified DNMT3A as the main DNA methyltransferase generating methylation of the ELP5 promoter and found that hypermethylation of the ELP5 promoter prevents the binding of the transcription factor PAX5 and represses PAX5-induced ELP5 transcription, highlighting a tumour suppressor role of PAX5 in GBC. This evidence concerns the gene ELP5 and neoplasm.