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A paper published by Liu and co-workers in a recent issue of Molecular Cancer not only reiterates the epigenetic silencing as a mechanism of GPER1 suppression, but also expands the scope of this emerging paradigm beyond breast cancer to include colorectal adenocarcinoma. This article is a commentary on the relevance and significance of their work. It presents results obtained through an independent analysis of TCGA-COADREAD dataset that supports their claim. It highlights the emerging role of DNA methylation in GPER1 regulation by drawing parallels with other published works, while at the same time draws attention of the readers to the caveats and the points of departures from recent literature.