PTCHD1 encodes a Patched-related protein with 12 transmembrane domains and a sterol-sensing domain, structurally similar to the Hh receptors PTCH1 and PTCH2, as well as the Niemann-Pick Type C1 protein (NPC1) and several others (fig. S5). Many Patched-related genes have been found in various organisms, from nematodes to humans, and they appear to play diverse biological functions, including cytokinesis, growth and pattern formation (33). For instance, there are just seven patched-related genes in humans (PTCH1, PTCH2, PTCHD1, PTCHD2, PTCHD3, NPC1 and c6orf138 (see fig. S5), whereas in C. elegans there are at least 26 patched-relaetd genes, with diverse roles in development in addition to Hh signaling, including cytokinesis, growth and pattern formation (33). In 10T1/2 cells, we have demonstrated an inhibitory effect of PTCHD1 on Gli-dependent transcription. Although these results suggest that PTCHD1 exhibits biochemical activity in Hh-dependent processes similar to that of PTCH1 and 2, other functions or roles for PTCHD1 cannot be excluded at this point.
