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pLGGs are a group of tumors for which the era of molecular diagnostics has truly shifted treatment paradigms and patient care. The discovery that this group of tumors is driven by single-gene alterations/fusions in the MAPK pathway has resulted in relatively rapid translation into targeted therapy options for patients with this often chronic disease. This translation has been facilitated through efforts of multiple collaboratives and consortia and has led to the development of clinical trials testing the role of targeted therapies in pLGG. Although these developments represent promise, many questions remain regarding these therapies including their long-term toxicities and their potential effects on the natural history of pLGG.