Class E vacuolar protein sorting (Vps) mutations cause yeast to generate a novel organelle - the class E compartment - next to the vacuole. The proteins affected by these mutations function in endosomal trafficking and have relatives in mammals, including the AAA-type ATPase SKD1. To investigate SKD1 function further, Hideaki Fujita and coworkers have used two-hybrid screening to search for its binding partners. They now reveal two new mammalian class E Vps proteins that bind to SKD1: SBP1 and mVps2 (see p. 2997). Both have orthologues in yeast and are targeted to aberrant endosomal structures in cells expressing ATPase-deficient SKD1. The authors' studies indicate that mVps2 controls membrane association of SKD1 and that SKD1 regulates assembly of a large SBP1-containing complex. Interestingly, SBP1 turns out to be identical to a previously isolated protein that interacts with the lysosomal trafficking regulator Lyst, mutations in which cause Chediak-Higashi syndrome (CHS). Fujita and co-workers also provide evidence that SKD1 can regulate membrane association of Lyst and that it is recruited to membranes by SBP1. Their findings thus point the way for new studies into the molecular mechanisms underlying formation of giant lysosomes in CHS.