The p24 proteins (p23, p24, p25 and p26) are an enigmatic family of transmembrane proteins that function early in the secretory pathway, localizing primarily to the Golgi. Their precise roles are controversial, partly because it is difficult to study proteins that both heterooligomerize and cycle between different membrane compartments. Jean Gruenberg and co-workers have got round the problem by generating a p25 mutant (p25SS) that lacks the normal KKXX ER-retrieval signal - the mutant escapes from the early secretory pathway, allowing examination of its behaviour in membranes that normally lack p24 proteins (see p. 4821). The authors observe that, in the presence of p25SS, other p24 proteins also escape the early secretory pathway, suggesting that p25 normally anchors them there. Combining advanced confocal microscopy and immunoelectron microscopy, they then demonstrate that p25SS ends up in late endosomes, in which it is confined to discrete membrane domains and interferes with cholesterol distribution. The p25SS domains are distinct from lipid rafts, exclude other transmembrane proteins and probably represent higher-order oligomers. Given this ability to exclude cholesterol, p25 could play an important role defining Golgi membrane domains and modulating their dynamics.