Dd-TRAP1 is a Dictyostelium homologue of TRAP-1, a human protein that binds to the type 1 tumor necrosis factor (TNF) receptor. TRAP-1 has a putative mitochondrial localization sequence and shows significant homology to members of the HSP90 family. Although TRAP-1 is mainly localized to mitochondria in several mammalian cells, in certain tissues it is also localized at specific extramitochondrial sites. In Dictyostelium cells, Dd-TRAP1 is predominantly located in the cell membrane/cortex during growth and just after starvation. Double staining of vegetatively growing cells with the anti-Dd-TRAP1 antibody and TRITC-phalloidin has demonstrated colocalization of Dd-TRAP1 and F-actin at the leading edge of cortical protrusions such as pseudopodes. Coupled with differentiation, however, Dd-TRAP1 located at the cortical region is translocated to mitochondria in spite of the absence of the mitochondrial localization sequence at its N-terminus. The translocation of this protein raises interesting and fundamental questions regarding possible mechanisms by which Dd-TRAP1 is involved in cellular differentiation.