Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at 'Leu-104', thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane (PubMed:27676298, PubMed:27528193). Ubiquitination of NFE2L1/NRF1 is a prerequisite for cleavage, suggesting that DDI2 specifically recognizes and binds ubiquitinated NFE2L1/NRF1 (PubMed:27528193). Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2 (Probable). Required, with DDI1, for cellular survival following replication stress. Together or redudantly with DDI1, removes RTF2 from stalled forks to allow cell cycle progression after replication stress and maintains genome integrity (PubMed:29290612). Homodimer (PubMed:27461074). Interacts with MCM6; PCNA; PSMD4; PSMD8; RPA2 and RPN2 (PubMed:29290612). Interacts with RTF2 (PubMed:29290612). Belongs to the DDI1 family. The protein was initially thought to be catalytically inactive (PubMed:27461074). It was later shown that it has aspartyl protease activity and mediates cleavage of NFE2L1/NRF1 (PubMed:27676298).