All eukaryotic SPTs studied to date are ER-resident and membrane bound with a heterodimeric protein core consisting of two subunits sharing ~20% identity: LCB1 and LCB2, ~53 and ~63 kDa respectively (Hanada, 2003; Denny et al. 2004; Han et al. 2004; Chen et al. 2006). The latter contains the canonical PLP cofactor binding site while the former has been suggested to be important for complex stability (Lowther et al. 2012). In contrast, the orthologous SPT from sphingomonad bacteria is a soluble 45 kDa homodimer (Ikushiro et al. 2001). SPT activity in apicomplexan parasites has been detected and was proposed as a potential drug target (Gerold & Schwarz, 2001; Bisanz et al. 2006; Coppens, 2013), however the enzyme(s) responsible have yet to be further characterized (Mina et al. 2017). In contrast, kinetoplastid parasites have been shown to possess a heterodimeric SPT similar to the mammalian orthologue (Denny et al. 2004). Inhibiting SPT activity (e.g. using myriocin, Fig. 2) results in various effects in different species. Mammalian cells exhibited a loss of viability, with a partial loss of SPT function resulting in a rare SL metabolic disease, Hereditary Sensory Neuropathy type I (HSN1) (Hanada, 2003). In contrast, Saccharomyces cerevisiae were found to be relatively tolerant (Nagiec et al. 1994), and Leishmania major lacking LCB2 were viable but unable to differentiate into infective metacyclic forms (Zhang et al. 2003). However, T. brucei procyclic forms in which SPT expression was reduced were non-viable (Fridberg et al. 2008).