Nr0b2, also known as Small Heterodimer Partner (SHP), is an orphan nuclear receptor acting as a transcriptional regulator. It controls various metabolic processes such as cholesterol and lipid homeostasis [3,4,5,6]. It is involved in pathways like FGF15/FGF19-NR0B2/SHP-TFEB which regulates postprandial lipids through lipophagy activation in the gut [4]. Its role in immune regulation and potential as a therapeutic target in cancer also highlight its biological importance [3,5].

In breast cancer, mice lacking Nr0B2 exhibit accelerated tumor growth as Nr0B2 in myeloid cells impairs the expansion of regulatory T cells (Tregs), a highly immune-suppressive subset, by decreasing aspects of the inflammasome and reducing IL1β [5]. In primary sclerosing cholangitis, Nr0B2 upregulation in cholangiocytes is independent of several factors, and its deregulation may lead to metabolic and premalignant reprogramming of cholangiocytes [2]. In gastric diseases, bioinformatics and Mendelian randomization analyses show a causal relationship between Nr0B2 expression and the risk of gastric cancer, gastric ulcer, and other gastritis, with low Nr0B2 expression being a risk factor for poor prognosis in gastric cancer [1].

In summary, Nr0B2 plays crucial roles in metabolic regulation, immune-tumor interactions, and disease development. Mouse models lacking Nr0B2 have revealed its significance in breast cancer progression, highlighting its potential as a therapeutic target. In addition, its role in gastric and liver-related diseases, as well as in lipid metabolism, underscores its importance in understanding disease mechanisms and developing treatment strategies [1,2,5].