WD40 repeat proteins have a wide range of diverse biological functions including signal transduction, cell cycle regulation, RNA splicing, and transcription. Here we report the identification and characterization of a novel human WD40 repeat protein, Monad. Monad is unique, since it contains only two WD40 repeats. Monad is widely expressed in human tissues with the highest expression in testis. Overexpression of Monad in HEK293 cells potentiated apoptosis and caspase-3 activation induced by tumor necrosis factor-alpha and cycloheximide. These results raise the possibility that Monad may function as a novel modulator of apoptosis pathway. (c) 2006 Elsevier Inc. All rights reserved.