As key players in normal physiology and in disease, it is unsurprising that there is a large body of evidence demonstrating the contribution of an imbalance in the SphK/S1P rheostat to a plethora of pathological conditions including cancer, diabetes, inflammatory diseases, neurodegenerative diseases (Parkinson's and Alzheimer's), cardiovascular and liver diseases, which have been extensively reviewed [2, 3, 11, 15, 18, 48, 56–72]. The gene discussed is SPHK1; the disease is diabetes mellitus.