Srebf2, short for sterol regulatory element-binding transcription factor 2, is a key regulator of cholesterol metabolism. It belongs to the SREBP family of transcription factors and controls the expression of enzymes involved in cholesterol synthesis [3]. Srebf2-related pathways are crucial for maintaining lipid homeostasis, and genetic models such as gene knockout studies can be used to explore its functions.

In various disease-related research, knockdown of Srebf2 in sorafenib-resistant HepG2 and Huh7 cells resensitized them to sorafenib, suggesting that Srebf2 promotes sorafenib resistance in hepatocellular carcinoma through the SREBF2-STARD4 axis [2]. In endothelial cells, LPS-induced Srebf2 expression, via the TLR4/JNK/c-Jun pathway, led to ER stress and Bax-mediated injury, and miR590-3p could alleviate this by negatively regulating Srebf2 [1]. In polycystic ovary syndrome, the rhythm gene PER1 promoted granulosa cell ferroptosis and abnormal lipid metabolism by inhibiting Srebf2 [4]. Also, in zebrafish, chemical inhibition or gene knockdown of srebf2 decreased optic nerve axon regeneration, indicating its importance in this process [5]. Pharmacological inhibition or RNA interference of Srebf2 attenuated liver cancer initiation in mice with gut flora disequilibrium [6].

In conclusion, Srebf2 is essential for cholesterol metabolism and lipid homeostasis. Model-based research, especially loss-of-function experiments, has revealed its significant roles in diseases such as hepatocellular carcinoma, endothelial cell injury, polycystic ovary syndrome, optic nerve regeneration, and liver cancer initiation. Understanding Srebf2 functions can provide potential therapeutic targets for these diseases.