Nuclear receptors control the transcriptional program of target cells and thereby their phenotype and activities. Two complementary studies by Micheals et al. (https://doi.org/10.1084/jem.20201311) and Chan et al. (https://doi.org/10.1084/jem.20200318) published in JEM uncover the cell type–specific expression and role of the nuclear receptors liver X receptors in the regulation of T cell homeostasis and function.