SPHK1 and type 1 diabetes mellitus: Although removal of one of the major SphK isozymes is not fatal, as determined in mice with knockout of either SphK1 or SphK2, what these studies have revealed is that loss of one isozyme increases the risk of major health problems including altered vasculature formation [73, 74], impairment in wound healing [75], abnormal islet formation, which could lead to type 1 diabetes [76], and cardiac dysfunction (ischemic) [77], among other complications.