Besides targeting of precursor polypeptides to the human endoplasmic reticulum (ER), mRNAs are targeted to the ER. While the first targeting process is reansonably well understood, relatively little is known about the latter. To obtain novel insights into mRNA targeting to the human ER, we combined siRNA-mediated depletion of putative mRNA-receptors of the ER-membrane in HeLa cells with label-free quantitative proteomics and differential expression analysis.