Crebl2, also known as cAMP response element-binding protein-like 2, is a bZIP_1 protein. It plays a role in multiple biological processes, being involved in pathways related to cell metabolism, adipogenesis, and fibrosis. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions [3].

In muscle and liver cells, Crebl2 knockdown in C2C12 myoblasts and Hepa1-6 hepatoma cells leads to increased glucose uptake, glycolysis, and triglyceride biosynthesis, suggesting its role as a regulator of cellular metabolism that links nutrient sensing via mTORC1 to the metabolic response of cells [1]. In hepatic fibrosis, HSCs-specific Crebl2 deletion ameliorates PTH-induced liver fibrosis, indicating that PTH1R signaling regulates collagen production in HSCs through the Crebl2/SMAD3/TGFβ regulatory circuits [2]. In 3T3-L1 adipocytes, CREBL2 knockdown restrains adipogenic conversion and lipogenesis, while its overexpression promotes adipogenesis via up-regulating PPARγ and C/EBPα [3]. In Schwann cells, miR-195-5p downregulates Crebl2, modulating Schwann cell functions and contributing to peripheral nerve regeneration [4].

In conclusion, Crebl2 is crucial in regulating cell metabolism, adipogenesis, hepatic fibrosis, and Schwann cell functions. The use of KO/CKO mouse models in these studies has revealed its role in disease-related processes such as liver fibrosis, providing insights into potential therapeutic targets for such diseases.