We then hypothesize the role CREB5-OLIG2 axis in GSCs as follows: 1) as a central nervous system (CNS) restricted transcription factor, it plays an essential role in glial progenitor proliferation [18–20]; (2) it is widely expressed in gliomas and plays a critical role in gliomagenesis and tumor phenotype plasticity; and [15–17, 21–23] (3) recently, OLIG2 has been identified as a core transcription factor, along with SOX2, SALL2, and POU3F2, that reprograms differentiated GBM cells into GSCs [14]. Here, CREB5 is linked to central nervous system cancer.