The cross-species differences encountered in the first, SPT-catalysed, step are mostly minor in terms of the chemical structure of the product; mainly due to the chain length of the acyl-CoA utilised in the reaction, e.g. myristoyl-CoA (in Leishmania spp. amongst other odd sphingoid base lengths (Hsu et al. 2007)) and palmitoyl-CoA, with the latter more predominant across the Eukaryota (in mammals, Plasmodium and T. brucei) (Richmond et al. 2010; Botté et al. 2013). Further differences may be apparent with respect to the catalysing enzyme, SPT (vide infra). However, clear divergence is observed in the second and the third steps, both of which represent a cell-fate modulator process. CerSs exhibit differential preferences for the chain length of the acyl-CoA substrate (Park et al. 2014) and its hydroxylation pattern (Layre & Moody, 2013), with 6 isoforms present in humans suggesting a different role for each CER species produced (Levy & Futerman, 2010; Figueiredo et al. 2012). To-date, one or, maximum, two genes encoding CerS function have been identified in protozoan parasite species (Koeller & Heise, 2011). However, most interesting is the variation in the complex SL formed in the Golgi, reflecting significant differences in the active site of the SL synthases catalysing the transfer reaction. The divergence of the protozoal complex SL synthases, and the synthetic products, with respect to the mammalian host, may provide opportunities to design selective inhibitors. Previously, this step has been validated as a promising drug target in fungi using aureobasidin A (AbA) (Fig. 2) (Denny et al. 2006).