Cholesteryl ester transfer protein (CETP) exists as full-length (FL) and exon 9 (E9)-deleted isoforms. Thefunction of E9-deleted CETP is poorly understood. Here, we investigated the role of E9-deleted CETP inregulating the secretion of FL-CETP by cells, and explored its possible role in intracellular lipid metabolism.CETP overexpression in cells that naturally express CETP confirmed that E9-deleted CETP is not secreted, andshow that cellular FL- and E9-deleted CETP form an isolatable complex. Co-expression of CETP isoformslowered cellular levels of both proteins, and impaired FL-CETP secretion. These effects were due to reducedsynthesis of both isoforms, however the predominate consequence of FL- and E9-deleted CETP co-expression isimpaired FL-CETP synthesis. We reported before that reducing both CETP isoforms or overexpressing FLCETP impairs cellular triglyceride storage. To investigate this further, E9-deleted CETP was expressed inSW872 cells that naturally synthesize CETP and in mouse 3T3-L1 cells that do not. E9-deleted CETPoverexpression stimulated SW872 triglyceride synthesis and increased stored triglyceride 2-fold. Expression ofE9-deleted CETP in mouse 3T3-L1 cells produced a similar lipid phenotype. In vitro, FL-CETP promotes thetransfer of triglyceride from endoplasmic reticulum-enriched membranes to lipid droplets. E9-deleted CETPalso promoted this transfer, although less effectively, and it inhibited the transfer driven by FL-CETP. Weconclude that FL- and E9-deleted CETP isoforms interact to mutually decrease their intracellular levels andimpair FL-CETP secretion by reducing CETP biosynthesis. E9-deleted CETP, like FL-CETP, alters cellulartriglyceride metabolism and storage but in a contrary manner