SEPS1 (also called selenoprotein S, SeIS, Tanis or VIMP) is a selenoprotein, localized predominantly in the ER membrane and also on the cell surface. In this report, we demonstrate that SEPS1 protein is also secreted from hepatoma cells but not from five other types of cells examined. The secretion can be abolished by the ER-Golgi transport inhibitor Brefeldin A and by the protein synthesis inhibitor cycloheximide. Using a sandwich ELISA, SEPS1 was detected in the sera of 65 out of 209 human subjects (31.1%, average = 15.7 +/- 1.1 ng/mL). Fractionation of human serum indicated that SEPS I was associated with LDL and possibly with VLDL. The function of plasma SEPS I is unclear but may be related to lipoprotein metabolism. (c) 2007 Elsevier Inc. All rights reserved.