Spinster homolog 2 (Spns2) is an S1P transporter belonging to the non-ATP-dependent organic ion transporter family. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that regulates the immune system, angiogenesis, auditory function, and epithelial and endothelial barrier integrity. Spns2 exports S1P to initiate lipid signaling cascades, playing a crucial role in lymphocyte trafficking, immune responses, and various physiological and pathological processes [1,3,4].

Global deletion of Spns2 (Spns2-/-) has been shown to reduce disease severity in several autoimmune disease models. Postnatal knockout of Spns2 (Spns2-Mx1Cre) also led to a significant reduction of pathogenic Th17 cells in the central nervous system, making these mice resistant to multiple sclerosis in experimental autoimmune encephalomyelitis models. These results suggest that lack of Spns2 affects S1P secretion and lymph node vasculatures, but blood vasculature remains normal. In macrophages, Spns2 deficiency enhances glycolysis, leading to increased intracellular lactate production and subsequent pro-inflammatory response. Reinforcing Spns2/S1P signaling can balance the immune response during sepsis [2,5].

In conclusion, Spns2 is essential for S1P-mediated signaling processes. Gene knockout mouse models, such as Spns2-/-and Spns2-Mx1Cre, have revealed its significant role in autoimmune diseases like multiple sclerosis and in sepsis. Understanding Spns2 function provides potential therapeutic targets for treating these and other related diseases.