ATRX, a guardian of chromatin

ATRX (alpha-thalassemia mental retardation X-linked) is one of the most frequently mutated tumor suppressor genes in human cancers, especially in glioma, and recent findings indicate roles for ATRX in key molecular pathways, such as the regulation of chromatin state, gene expression, and DNA damage repair, placing ATRX as a central player in the maintenance of genome stability and function. This has led to new perspectives about the functional role of ATRX and its relationship with cancer. Here, we provide an overview of ATRX interactions and molecular functions and discuss the consequences of its impairment, including alternative lengthening of telomeres and therapeutic vulnerabilities that may be exploited in cancer cells.