We hypothesized that EPAC might act on RIM1 through the Rap1-PLCε-PKCε module (Figure 1G), which is shown to be activated by EPAC in neuroblastoma cells (Schmidt et al., 2001), dorsal root ganglion neurons (Hucho et al., 2005), as well as heart cells (Oestreich et al., 2009). The gene discussed is RAPGEF4; the disease is neuroblastoma.