Ceramide kinase (CERK) is a mammalian lipid kinase that phosphorylates ceramide to produce ceramide-1-phosphate (C1P) [4,5]. C1P is involved in various biological processes such as membrane biology, regulation of membrane-bound proteins, and acts as a signaling entity [5]. It has been associated with multiple pathways including those related to cell survival, lipid metabolism, and redox homeostasis [4]. Genetic models like CERK-knockout mice are valuable for studying its functions [1].

In a study using CERK-knockout mice, it was found that CERK-derived C1P plays a protective role against high-altitude pulmonary edema (HAPE). Inhibition of CERK exacerbated HAPE induced by a hypobaric hypoxic environment. CERK inhibition led to aryl hydrocarbon receptor nuclear translocator-like (ARNTL) autophagic degradation, disrupting the circadian rhythm and triggering mitochondrial damage. Exogenous C1P prevented ARNTL degradation, alleviated mitochondrial damage, and relieved HAPE [1]. In breast cancer, overexpression of CERK was associated with nodal metastasis, late tumor stage, high proliferation potency, and poor patient survival. Computational network analysis showed its association with metastasis and drug-resistance markers [2]. In mutant KRAS non-small cell lung cancer (NSCLC), inhibition of CERK induced ferroptosis, and it synergized with cisplatin in reducing cell survival and in vivo tumor growth [3].

In conclusion, CERK is crucial in maintaining physiological functions through its role in producing C1P. Model-based research, especially using CERK-knockout mouse models, has revealed its significance in diseases such as HAPE, breast cancer, and NSCLC. Understanding CERK functions provides potential therapeutic targets for these diseases.