IRE1 alpha is an ER-located transmembrane RNase whose activation leads to the production of the transcriptional factor, XBP1. Recently, many studies report that IRE1 alpha-XBP1 pathway has novel and significant roles in placenta. However, its molecular details have been still unknown. To address this point, we have focused on the molecular linkage between IRE1 alpha-XBP1 pathway and Cts7 and Cts8, which are essential cathepsins for placenta formation. In cellular model, this pathway positively contributed to their expression at transcriptional level. In addition, the disruption of IRE1 alpha or XBP1 in animal model significantly attenuated their transcripts in placenta. These results indicated that IRE1 alpha-XBP1 pathway function as a specific program supporting the placenta formation by ensuring the moderate expression of specific subset of placental cathepsins. (C) 2013 Elsevier Inc. All rights reserved.