The functional properties of a novel protein, protein disulfide isomerase-related protein A (PRPA) from Aspergillus niger T21 have been characterized. (1) PRPA possesses disulfide isomerase activity. (2) In Hepes buffer, at substiochiometric concentrations, PRPA facilitates the formation of inactive lysozyme aggregates associated with PRPA (anti-chaperone activity); while at a high molar excess PRPA inhibits aggregation by maintaining lysozyme in a soluble, yet inactive, state (chaperone-like activity). However, PRPA only exhibits chaperone-like activity during lysozyme refolding in phosphate buffer. (3) Experiments have indicated that disulfide cross-linkage is not required for the interaction between PRPA and lysozyme, and hydrophobic interaction may be responsible for PRPA effect on lysozyme. (4) Co-expression of PRPA and prochymosin in Escherichia coli leads to reduction of inclusion bodies, rendering part of prochymosin molecules soluble yet inactive. The structural and functional characteristics of PRPA suggest that PRPA may play an important role in protein folding, aggregation, and retention in the endoplasmic reticulum. (C) 2004 Elsevier Inc. All rights reserved.