Members of the low-density lipoprotein (LDL) receptor family have dual roles in endocytosis and signalling. Megalin, for example, mediates endocytic uptake of vitamin D metabolites in the kidney and also appears to act as a receptor for sonic hedgehog during forebrain development. Quite how such receptors combine their endocytic and signalling roles is unclear, but adaptor proteins containing PTB domains, PDZ domains or ankyrin repeats are thought to play a part. Thomas Willnow and co-workers have used a two-hybrid approach to identify a novel class of megalin adaptor: megalin-binding protein (MegBP). MegBP is a 350-residue protein that contains two tetratrico peptide repeats(motifs implicated in protein—protein interactions) and binds to a proline-rich region in the megalin cytoplasmic tail (see p. 453). The authors show that MegBP functionally interacts with megalin in vivo. Moreover, they find that it also binds to a variety of signalling molecules and transcriptional regulators. Interestingly, these include SKI-interacting protein (SKIP), a coactivator for the vitamin D receptor. An attractive hypothesis is therefore that MegBP acts by sequestering transcription factors involved in megalin signalling and releasing them after endocytic uptake of incoming ligands.