Nr3c2, encoding the mineralocorticoid receptor (MR), is crucial for maintaining electrolyte and fluid balance by mediating the effects of aldosterone in the kidney and other tissues [1]. It is involved in pathways related to inflammation, metabolism, and cell growth regulation. Genetic models, such as KO/CKO mouse models, could potentially help in understanding its functions in vivo.

Nr3c2 haploinsufficiency due to microdeletions in NR3C2 is an under-recognized cause of pseudohypoaldosteronism type 1A (PHA1A) [1]. In pancreatic cancer, the MIF/NR3C2 axis regulates glucose metabolism reprogramming through MAPK-ERK and AP-1 pathways [2]. In invasive breast carcinoma, high NR3C2 expression is associated with better patient survival, and enriched pathways include neuroactive ligand-receptor interaction [3]. In human coronary endothelial cells, NR3C2 promotes NLRP3-induced inflammatory responses in ox-LDL-induced inflammation [4]. In colorectal and colon cancer, NR3C2 inhibits cell proliferation, invasion, and angiogenesis through various signaling pathways like regulating glucose metabolism, phosphorylating AMPK, and affecting the Wnt/β-Catenin and AKT/ERK signaling pathways [5,6,7]. In ischemic cerebral infarction, NR3C2 activates LCN2 transcription to promote endoplasmic reticulum stress and cell apoptosis [8].

In conclusion, Nr3c2 is essential for maintaining electrolyte balance and also plays significant roles in various disease-related biological processes including metabolism, inflammation, and cell growth. Research using gene knockout models could further enhance our understanding of Nr3c2 functions in these disease areas, potentially leading to new therapeutic strategies for conditions such as PHA1A, pancreatic cancer, breast cancer, coronary artery disease, colorectal and colon cancer, and ischemic cerebral infarction.