Sphk1, sphingosine kinase 1, is a key enzyme phosphorylating sphingosine to sphingosine 1-phosphate (S1P). S1P is a bioactive lipid involved in multiple cellular processes, and the SphK1-S1P axis is associated with various signaling pathways [3]. Genetic models, like KO mouse models, are valuable for studying SphK1's function.

Sphk1 deficiency protects mice from acetaminophen-induced ER stress and mitochondrial permeability transition, alleviating liver damage and inflammation [1]. In atherosclerosis, SphK1 deficiency ameliorates the disease by inhibiting the S1P/S1PR3/Rhoa/ROCK pathway, reducing lipid accumulation and vascular permeability [5]. In cerebral ischemia/reperfusion injury, knockdown of SphK1 suppresses inflammation and cell death [2]. Also, SphK1-induced autophagy in microglia promotes neuronal injury following cerebral ischemia-reperfusion [6]. In head and neck squamous cell carcinoma (HNSCC), SPHK1 promotes tumor growth and immune evasion by regulating the MMP1-PD-L1 axis [4].

In conclusion, SphK1 plays essential roles in multiple biological processes and disease conditions. Gene knockout mouse models have revealed its contributions to drug-induced liver injury, atherosclerosis, cerebral ischemia/reperfusion injury, and cancer. Understanding SphK1's functions provides insights into disease mechanisms and potential therapeutic targets for these diseases.