Nature Cell Biology, Published online: 20 August 2026; doi:10.1038/s41556-026-02046-z Long recognized for its roles in autophagy and endosomal trafficking, phosphatidylinositol 3-kinase class III (PI3K-3) is now shown to also function in the nucleus. A recent study shows that PI3K-3 associates with the transcriptional machinery and a chromatin-modifying complex, and contributes to transcriptional adaptation during fasting.