SLs can also function as bioactive signalling molecules due to their biophysical properties, e.g. the low pKa (7–8) of SPH allows it to remain partially uncharged at physiological pH retaining the ability to move across membranes (Merrill & Sandhoff, 2002). Likewise, CER, a neutral species, is able to freely flip flop across membranes (Hannun & Obeid, 2008). Many studies have produced evidence of such signalling functions, e.g. SPH exerts pleiotropic effects on protein kinases; CER mediates many cell-stress responses, including the regulation of apoptosis (Georgopapadakou, 2000); and S1P has crucial roles in cell survival, cell migration and inflammation (Hannun & Obeid, 2008)