Nr1h2, also known as LXRβ, is a member of the nuclear hormone receptor superfamily of ligand-dependent transcription factors. It acts as a “cholesterol sensor” to regulate lipid homeostasis, playing a key role in cholesterol and fatty acid metabolism. It is activated by cholesterol derivatives and is involved in various physiological processes [4,6].

In the context of diseases, Nr1h2 has been implicated in multiple conditions. In ovarian cancer, the presence of NR1H2+IRF8+ macrophage clusters in the high T-cell infiltration group suggests an anti-tumor response [1]. In stress-induced depression, short-term stress may induce cholesterol metabolism disorders by activating the NR3C1/NRIP1/NR1H2 signaling pathway, which impairs neuronal synaptic plasticity and participates in depressive-like behavior in mice [2]. Polymorphisms in Nr1h2 are associated with an increased risk of type 2 diabetes mellitus, preeclampsia, and may also be related to insulin secretion in subjects at high risk of type 2 diabetes, as well as potentially contributing to the risk of Alzheimer's disease [3,5,7,8]. In addition, Nr1h2 plays a crucial role in blastoid formation, and its activation can rewire conventional embryonic stem cells into a distinct pluripotency state [9].

In conclusion, Nr1h2 is essential for lipid homeostasis and is involved in multiple disease-related processes such as cancer, depression, diabetes, preeclampsia, and Alzheimer's disease. The study of Nr1h2, especially through genetic models, has provided valuable insights into the molecular mechanisms underlying these diseases, which may help in developing targeted therapeutic strategies.