Complexin Membrane Interactions: Implications for Synapse Evolution and Function

•The critical SNARE-binding protein complexin (Cpx) interacts with membranes via its C-terminal domain.•Both CAAX and non-CAAX variants of Cpx evolved from an ancestral CAAX protein.•Non-CAAX Cpx variants contain a curvature-sensing amphipathic domain required for localization.•The amphipathic region of mammalian Cpx can remodel and perforate membranes in vitro.