Epithelial membrane protein 2 (EMP2) is a cell surface protein that has recently emerged as an object of neuro-oncological interest due to its potential to be utilized as a biomarker and target for antibody therapies. Preclinical studies have demonstrated that EMP2 is associated with disease prognosis in a number of human cancers, including glioblastoma. The four large extracellular domains of EMP2 and its association with the extracellular matrix makes it an attractive target for future cancer therapies. Translational research suggests that EMP2 may be targeted with antibodies to improve tumor control and survival in a variety of murine models and cancer types. However, in order to translate these preclinical findings into the clinic, future research will need to focus on elucidating the role EMP2 in the normal human body by better understanding its molecular and chemical interactions. The focus of this review is to provide a comprehensive insight into current research endeavors, discuss the potential for clinically translatable applications, and predict the future directions of such research.