SphK2, short for sphingosine kinase 2, phosphorylates sphingosine to sphingosine 1‑phosphate (S1P), a bioactive lipid mediator. SphK2 is involved in multiple pathways, such as histone acetylation regulation, which impacts gene transcription, and is crucial for biological processes like cell proliferation, differentiation, and apoptosis [1,3,4,5]. Gene knockout models, especially SphK2 -/- mice, are valuable tools in studying its functions.

In a SphK2 knockout mouse model, loss of SphK2 inhibited hypoxic-induced pulmonary hypertension (PH) and histone H3K9 acetylation, indicating that SphK2 promotes PH through regulating histone acetylation in pulmonary artery smooth muscle cells [1]. In aging SphK2 -/- mice, they were protected from obesity and insulin resistance, suggesting SphK2 has a role in glucose and lipid metabolism [4]. In RAW264.7 and THP-1 cells, knockdown of SphK2 via shRNA decreased lipopolysaccharide-induced M1 macrophage polarization, oxidative stress, and NLRP3 inflammasome activation, demonstrating its role in acute lung injury [2].

In conclusion, SphK2 plays essential roles in various biological processes, including those related to PH, acute lung injury, heart regeneration, obesity, and insulin resistance. The use of SphK2 knockout mouse models has significantly contributed to understanding its functions in these disease areas, providing potential therapeutic targets for related diseases.