Isx, short for intestine-specific homeobox, is an intestine-specific transcription factor. It participates in the maintenance of vitamin A metabolism by regulating the expression of beta-carotene 15,15'-monooxygenase (Bcmo1) [4]. Relaxing the regulation of SR-B1 expression in enterocytes by genetic deletion of Isx enhances zeaxanthin accumulation in tissues, suggesting its role in carotenoid metabolism [5].

In the context of chronic hepatitis C virus (HCV) infection, the HCV core protein-ISX axis promotes a spectrum of metabolic, fibrogenic, and immune modulators, regulating HCV-infection relevant pathogenic phenotypes in vitro and in vivo. Transgenic mice with this axis show enhanced metabolic disturbance, immune suppression, and chronic liver fibrosis [2]. In lung cancer, PCAF-mediated acetylation of ISX recruits BRD4, promoting epithelial-mesenchymal transition (EMT) and cancer metastasis. Ectopic ISX expression in lung cancer cells enhances EMT marker expression and induces metastasis [1,3].

In conclusion, Isx plays essential roles in vitamin A and carotenoid metabolism. Its involvement in disease-related processes such as HCV-induced chronic liver disease and lung cancer metastasis, as revealed through in vivo studies including mouse models, highlights its significance. Understanding Isx's functions could potentially lead to new therapeutic strategies for these diseases.