CLPP and neoplasm: ONC201, a dopamine D2 receptor (DRD2) antagonist and caseinolytic protease proteolytic subunit (ClpP) agonist, has been shown to activate DR5/TRAIL-mediated apoptosis, as well as other anti-proliferative transcriptional programs, in tumor cells.62,63 The prognostic importance of ClpP in pediatric gliomas, as well as the ability of this drug to cross the intact BBB, has made it of therapeutic interest in DMG patients.64–66