Simple SummaryMethyl-CpG binding protein 2 (MeCP2) is a nuclear protein that is mainly studied for its role as an epigenetic regulator of gene transcription. Gene mutations affecting the function or expression level of this epigenetic regulator, particularly in the brain, have been associated with a variety of human neurological and neurodevelopmental disorders. However, recent studies suggest that MeCP2, while being an epigenetic reader, also plays a role in the development and/or progression of several types of human cancer. This review provides a general overview of current research into the proposed molecular pathways involving MeCP2 as an emerging oncogene in human cancers and/or cancer cell lines, and highlights potential therapeutic targets in cancer biology.AbstractEpigenetic mechanisms are gene regulatory processes that control gene expression and cellular identity. Epigenetic factors include the “writers”, “readers”, and “erasers” of epigenetic modifications such as DNA methylation. Accordingly, the nuclear protein Methyl-CpG-Binding Protein 2 (MeCP2) is a reader of DNA methylation with key roles in cellular identity and function. Research studies have linked altered DNA methylation, deregulation of MeCP2 levels, orMECP2gene mutations to different types of human disease. Due to the high expression level of MeCP2 in the brain, many studies have focused on its role in neurological and neurodevelopmental disorders. However, it is becoming increasingly apparent that MeCP2 also participates in the tumorigenesis of different types of human cancer, with potential oncogenic properties. It is well documented that aberrant epigenetic regulation such as altered DNA methylation may lead to cancer and the process of tumorigenesis. However, direct involvement of MeCP2 with that of human cancer was not fully investigated until lately. In recent years, a multitude of research studies from independent groups have explored the molecular mechanisms involving MeCP2 in a vast array of human cancers that focus on the oncogenic characteristics of MeCP2. Here, we provide an overview of the proposed role of MeCP2 as an emerging oncogene in different types of human cancer.