SPTs are members of the pyridoxal 5′-phosphate (PLP)-dependent (Sandmeier et al. 1994) α-oxoamine synthase family and share a conserved motif (T[FL][GTS]K[SAG][FLV]G) around the PLP-binding lysine (in bold) (Young et al. 2012). SPT catalyses the first rate-limiting step in the de novo biosynthesis of SLs (Weiss & Stoffel, 1997; Hojjati et al. 2005) (Fig. 2), a reaction involving the decarboxylative Claisen-like condensation of serine and an acyl-CoA (Lowther et al. 2012), to yield the sphingoid base backbone, 3-ketodihydrosphingosine (3-KDS) (Hanada, 2003; Raman et al. 2009; Lowther et al. 2012). Therefore, SPT represents the ‘Gatekeeper’ of the SL biosynthetic pathway.