The emerging focus on epigenetic regulation in cancer biology has unveiled the significant role of CXorf67, a protein encoded by a gene on the X chromosome. CXorf67 interacts with core components of PRC2, namely EZH2 and SUZ12, thereby influencing histone modifications like H3K27me3. Research indicates that CXorf67 is overexpressed in specific malignancies, including posterior fossa ependymomas, diffuse midline glioma, endometrial stromal sarcoma, non-small cell lung cancer, and Merkel cell carcinoma. In posterior fossa ependymomas and diffuse midline glioma, CXorf67 mimics the oncogenic histone H3K27M, inhibiting PRC2 function and altering chromatin states. In endometrial stromal sarcoma, CXorf67 forms fusion genes with MBTD1, potentially disrupting polycomb group (PcG) functions. Additionally, CXorf67’s interaction with PALB2 affects the BRCA1-PALB2-BRCA2 complex, influencing DNA repair mechanisms. These findings highlight CXorf67’s dual role in epigenetic regulation and DNA damage response, suggesting its potential as a therapeutic target. However, further research is needed to explore its functions in other cancers and clarify its molecular mechanisms. Our review synthesizes current knowledge on CXorf67’s biological significance, particularly in epigenetics and DNA damage, and its implications in oncogenesis.

The growing interest in post-translational protein modification, particularly in SUMOylation, is driven by its crucial role in cell cycle regulation. SUMOylation affects various cell cycle regulators, including oncogenes, suggesting its relevance in cancer. SUMO E3 ligases are pivotal in this process, exhibiting diverse functionalities through structural domains and subcellular localizations. A less-explored SUMO E3 ligase, RANBP2, a component of the vertebrate nuclear pore complex, emerges as a central player in cellular cycle processes, as well as in tumorigenesis. The current studies illuminate the importance of RANBP2 and underscore the need for more extensive studies to validate its clinical applicability in neoplastic interventions. Our review elucidates the significance of RANBP2 across various types of malignancies. Additionally, it delves into exploring RANBP2 as a prospective therapeutic target for cancer treatment, offering insights into the avenues that scholars should pursue in their subsequent research endeavors. Thus, further investigation into RANBP2’s role in solid tumorigenesis is eagerly awaited.