The translocon-associated protein (TRAP, also termed the signal sequence receptor) complex is required for the efficient translocation of secretory and membrane proteins in the endoplasmic reticulum, and is also involved in the endoplasmic reticulum stress-mediated unfolded protein response pathway. To investigate the roles of Trap-γ, a TRAP complex subunit, we generated Trap-γ knockout mice and found that mutant pups died soon after birth because of retarded embryonic organ growth, especially in the lung. The mutant placentae showed severe vascular network malformation in the labyrinth and significant reductions in blood space areas, which had an adverse effect on intrauterine embryonic growth. Placental malformation was already found by the mid-gestation-stage mutant placenta, with poor vascular endothelial cell proliferation in the chorionic plate region and increased apoptotic cell death in the labyrinth. Thus, Trap-γ appears to be required for vascular network formation in murine placental development. Developmental Dynamics 240:394–403, 2011. © 2011 Wiley-Liss, Inc.