CMTM is a novel family of proteins linking chemokines and TM4SF. Several members of this family are highly expressed in testes and regulate androgen receptor (AR) transcription activity. One member of this family, CMTM3, has the highest expression level in testes and contains one leucine zipper and two LXXLL motifs. As assessed with the dual-luciferase reporter assay, overexpression of CMTM3 represses AR transactivation, while knocking down it can increase AR transactivation. Moreover, CMTM3 inhibits prostate-specific antigen (PSA) expression in LNCaP cells at both mRNA and protein levels with no obvious influence on AR expression. Taken together, CMTM3 may play some roles in the maturation and maintenance of the male reproduction. (c) 2008 Elsevier Inc. All rights reserved.