Ckmt1, or creatine kinase ubiquitous-type, mitochondrial, is a mitochondrial isozyme of creatine kinases that play a crucial role in energy metabolism. It is involved in processes such as the phosphocreatine energy shuttle and oxidative phosphorylation, which are vital for maintaining mitochondrial homeostasis and cellular energy balance [4,6].

In inflammatory bowel disease (IBD), neutrophil-derived PAD4 can citrullinate CKMT1 at the R242 site in intestinal epithelial cells (IECs), reducing its protein stability via the autophagy pathway. This leads to compromised mitochondrial homeostasis, impaired intestinal barrier integrity, and IEC apoptosis. IEC-specific depletion of CKMT1 exacerbates intestinal inflammation and apoptosis in colitis mice, highlighting its importance in maintaining intestinal homeostasis [1].

In white/beige adipose tissue, CKMT1 is dispensable for mitochondrial bioenergetics and the regulation of energy expenditure, as shRNA-mediated reduction in cultured adipocytes and ablation in mice did not show significant effects on related processes [2].

In breast cancer, while CKMT1 is highly expressed in primary tumors and promotes cell viability, its downregulation in metastasis drives up mitochondrial reactive oxygen species (ROS) levels, contributing to cell migration and invasion [3].

In nasopharyngeal carcinoma, overexpression of CKMT1 promotes cell proliferation and migration, and affects radiosensitivity by regulating STAT3 phosphorylation [5].

In the context of osteoclastogenesis in rheumatoid arthritis, MTHFD2 promotes it by enhancing CKMT1-mediated oxidative phosphorylation [6].

In summary, Ckmt1 is essential for maintaining mitochondrial function and cellular energy-related processes. Gene-knockout (KO) and conditional-knockout (CKO) mouse models have revealed its significance in various disease conditions such as IBD, breast cancer, nasopharyngeal carcinoma, and rheumatoid arthritis, providing potential therapeutic targets for these diseases.