IP3-mediated cellular Ca2+ signaling is organized as a hierarchy, wherein global, cell-wide signals, such as those discussed above, arise by recruitment of local, ‘elementary' events involving individual IP3R channels or clusters of small numbers of IP3Rs.34, 52 We therefore imaged these elementary events to elucidate how deficits in the global Ca2+ signals in FXS and TS cells may arise at the level of local IP3R clusters. Here, ITPR1 is linked to Timothy syndrome.