POT1 is a member of the shelterin complex, which binds telomeres and regulates their extension. Germline mutations in POT1 confer increased risk to a host of cancers, including glioma. Using native mouse models of glioma, it was found that deletion of POT had sex-specific effects on tumorigenesis, with females exhibiting decreased survival compared to males. Transcriptomic analysis and immunostaining validation studies revealed sex-specific changes in immune populations, with females exhibiting decreased expression of microglia/macrophage markers. Artwork by Emma Vidal. For details, see article by Jalali and colleagues on page 2703.