The high degree of conservation in the IncE binding surface of SNX5 implies that this site is critical for the normal function of SNX5 and its homologs. Previously, the expression of a GFP-tagged IncE C-terminal domain was shown to interfere with the SNX5/SNX6-dependent retrograde trafficking of the cation-independent mannose-6-phosphate receptor (CI-MPR) (Mirrashidi et al., 2015). Combined with our structural data, this infers that IncE is mimicking and interfering with SNX5/SNX6-mediated protein interactions, with a ligand(s) required for normal endosomal trafficking that remains to be discovered. Once recruited to the inclusion, SNX-BAR proteins are localized to the bulk membrane and dynamic tubules. While it is logical to imagine they could play a positive role in the sculpting of the inclusion, this is somewhat difficult to reconcile with the effect of SNX5 and SNX6 knockdown, which results in an increased production of C. trachomatis infectious progeny. Alternatively, although a pool of SNX5/SNX6 and associated SNX1/SNX2 proteins remain on endosomes in C. trachomatis infected cells, their sequestering by the chlamydial inclusion may interfere with normal endosomal trafficking (Figure 7D). It was thus proposed that the role of IncE could be to compete for SNX-retromer endosomal interactions, resulting in the breakdown of normal trafficking of the CI-MPR and lysosomal hydrolases and hence perturbation of the endolysosomal system’s capacity for bacterial destruction (Aeberhard et al., 2015; Mirrashidi et al., 2015). Defining the precise role of SNX proteins and other endocytic machinery in chlamydial infection will clearly require further study.