Mlx, also known as Max-like protein X, is a key component in a transcriptional network parallel to the Myc/Max/Mad network. It functions as a heterodimer binding partner for glucose-sensing transcription factors like ChREBP and MondoA. Mlx is involved in multiple metabolic pathways, including lipid and glucose metabolism, and plays a crucial role in maintaining redox balance, and nutrient-sensing mechanisms [2,3,4,5,6]. Genetic models, such as knockout mouse models, are valuable for studying its functions.

In osteosarcoma, knockdown of MLX impairs tumor growth and metastasis, and disrupts redox balance by affecting SLC7A11-mediated cysteine uptake, leading to ferroptosis [1]. In hepatocellular carcinoma, liver-specific knockout of Mlx decreases lipogenic gene expression, lipid levels, and blocks tumorigenesis in multiple models, highlighting its role in the glucose-induced lipogenic program promoting HCC development [3]. In primary human hepatocytes, MLX knockdown alters lipid and glucose metabolism, favoring catabolism over anabolism [2].

In conclusion, Mlx is essential for regulating lipid and glucose metabolism, redox balance, and plays a significant role in diseases like osteosarcoma and hepatocellular carcinoma. The use of KO/CKO mouse models has been instrumental in revealing these functions, providing insights into potential therapeutic targets for these diseases.