We have identified the saponin-domain containing protein Tb927.5.1160 as a novel endoplasmic reticulum (ER) factor in Trypanosoma brucei. Tb927.5.1160 acts proximal to the prototypic ER chaperon BiP, the conserved heat shock protein 70 family chaperon playing a key role in protein folding and ER quality control, and exhibits a conserved BiP binding region shared with the mammalian BiP nucleotide exchange inhibitor MANF (mesencephalic astrocyte-derived neurotrophic factor). We demonstrated by inducible RNAi depletion and over-expression that Tb927.5.1160 has a marked effect on the sensitivity toward ER-stress and is essential for T. brucei viability. Here we deposit whole cell proteomics data monitoring protein abundance changes after 48 hours induction of Tb927.5.1160 RNAi in bloodstream form (BSF) and procyclic-form (PCF) T. brucei, and Tb927.5.1160 overexpression in BSF.