Significance Pregnancy is a unique physiological state involving biological stresses that promote protein damage (misfolding) within the maternal body. Currently, little is known regarding how the maternal body copes with elevated protein misfolding in pregnancy. This is important, because the accumulation of misfolded proteins underlies many human disorders, including preeclampsia, a serious complication of pregnancy. In this study, we show that pregnancy zone protein (PZP) efficiently inhibits the aggregation of misfolded proteins, including the amyloid beta peptide, which forms plaques in preeclampsia and in Alzheimer’s disease. We propose that up-regulation of PZP is a major maternal adaptation that helps to maintain protein homeostasis during pregnancy. Moreover, pregnancy-independent up-regulation of PZP indicates that its chaperone function could be broadly important in humans.