Melanopsin is an atypical opsin protein required in vertebrates to mediate nonvisual responses to light, including regulation of circadian behavior and pupil constriction. Panda et al. report that, when expressed in Xenopus oocytes, melanopsin activates heterotrimeric G protein signaling pathways characteristic of invertebrate opsins in response to light. Melanopsin could also activate mammalian TRPC channels, whose paralogs in Drosophila serve as phototransduction channels. Thus, an invertebrate signaling system appears to be preserved in the mammalian retina.