Crtc2, also known as CREB-regulated transcription coactivator 2 or TORC2, is a transcriptional coactivator of CREB (cAMP response element binding protein). It affects human energy metabolism through pathways such as the cyclic adenosine phosphate pathway and the mTOR pathway. Crtc2 is associated with key metabolic processes like glucose and lipid metabolism, and its study using gene knockout (KO) or conditional knockout (CKO) mouse models can reveal its in-vivo functions [2].

In KO mouse models, studies have shown that Crtc2 plays diverse roles. In the liver, it controls lipid metabolism by regulating SREBP1. mTOR phosphorylates Crtc2 to modulate COPII-dependent SREBP1 processing, and overexpressing an mTOR-defective Crtc2 mutant in obese mice improves the lipogenic program and insulin sensitivity [1]. Also, Sam68 promotes hepatic gluconeogenesis via Crtc2. Sam68 interacts with and stabilizes Crtc2, and deletion of Sam68 reduces Crtc2 protein levels, blood glucose, and glucagon-induced gluconeogenic gene expression [3]. In addition, in hepatocellular carcinoma, DNA promoter hypomethylation leads to increased Crtc2 expression, which contributes to malignant phenotypes and primary resistance to immunotherapy through the Wnt/β-catenin pathway, and targeting Crtc2 may enhance immunotherapy response [4].

In conclusion, Crtc2 is a crucial regulator in energy metabolism, especially in glucose and lipid metabolism. Studies using KO/CKO mouse models have demonstrated its roles in various disease conditions, including obesity-related metabolic disorders and hepatocellular carcinoma. These findings provide insights into potential therapeutic strategies targeting Crtc2 for treating related diseases.