Only about 2% of the human genome encodes for proteins; the biomedical research was, nevertheless, until recently, almost exclusively focused on this tiny fraction of the genome. The majority of the human genome is transcribed to non-protein-coding RNA (ncRNA), which is often considered as the “dark matter” or junk material. However, ncRNAs play diverse regulatory roles and represent critical elements that make humans highly complex and distinct from other animals. These regulatory elements are essential for normal physiologic functions and frequently dysregulated in disease. The brain, the most complex of human organs, is characterized by the extreme number and diversity of ncRNA species. Our Laboratory investigates various classes of ncRNA, such as microRNA, lncRNA, and enhancer RNA, involved in the pathogenesis of malignant brain tumors and neurodegenerative diseases (e.g., Alzheimer’s disease). Our research ranges from understanding the basic biology of ncRNA to the development of novel ncRNA-targeting therapeutic strategies for neurologic diseases.