Ndrg1, short for N-myc downstream regulated gene 1, has diverse functions. It is involved in various biological processes such as angiogenesis, cell proliferation, and differentiation [4]. It is associated with multiple pathways including PI3K/Akt/mTOR [4], and its dysregulation is linked to several diseases, especially cancers. Genetic models, like gene knockout mouse models, are valuable for studying its functions.

In fasting, activation of mTORC2 leads to Ndrg1 phosphorylation at serine 336, which is crucial for mitochondrial fission and respiratory sufficiency. Ndrg1-deficient cells display mitochondrial phenotypes similar to fission failure [1]. In cancer, Ndrg1 shows context-dependent roles. For instance, in pancreatic ductal adenocarcinoma, Ndrg1 overexpression or pharmacologic activation upregulates MHC-1, promoting CD8+ T cell infiltration and overcoming immunotherapy resistance [2]. In gastric cancer patient-derived organoids, inhibition of KDM1A, which represses Ndrg1, causes organoid growth retardation, and Ndrg1 upregulation predicts response to KDM1A inhibitors [3]. In hypoxia-induced pulmonary hypertension, Ndrg1 affects the proliferation, apoptosis, and migration of pulmonary artery smooth muscle cells via DRP1 and PI3K/Akt/mTOR signaling pathways [4].

In conclusion, Ndrg1 is essential in processes like mitochondrial fission during fasting and has complex roles in cancer and hypoxia-related diseases. Gene knockout and related models have significantly contributed to understanding its functions in these disease areas, providing insights into potential therapeutic strategies for conditions such as cancer and pulmonary hypertension.