TCTP, is an essential component of the tuberous sclerosis-RHEB pathway. Reducing Drosophila Tctp levels reduced cell size, cell number, and organ size, which mimics Drosophila Rheb mutant phenotypes. Drosophila Tctp is genetically epistatic to Tsc1 and Rheb, but acts upstream of S6K, a downstream target of Rheb. Drosophila Tctp directly associated with Rheb and displayed guanine nucleotide exchange activity with it in vivo and in vitro. Human TCTP showed similar biochemical properties compared to Drosophila Tctp and could rescue Drosophila Tctp mutant phenotypes, suggesting that the function of TCTP in the TSC pathway is evolutionarily conserved. Overexpression of TSAP6 increased the level of TPT1 in exosome preparations and consistently enhanced TPT1 secretion.