IP3 is an important second messenger to release Ca2+ from internal store. IP3receptor (IP3R) works as an IP3 induced Ca2+ release channel and requires IP3 and Ca2+ as coagoinist. We found IP3R is involved in fertilization, meiosis and mitosis by using a specific antibody. We further found that IICR is essential for determination of dorsoventral axis formation. Neuronal type 1 IP3R-deficient mice generated by a gene-targeting technique exhibit a significant reduction of birth rate and abnormal behavior (ataxia and seizure). Long-term depression of the cerebellum was blocked in the type 1 IP3R-deficient mice. Long-term potentiation (LTP) of CA1 hippocampus was enhanced but depotentiation and LTP suppression was reduced in IP3R1-deficient mice. These evidences suggest that IICR is involved in neuronal plasticity. The coupling mechanism between ER Ca2+ stores and plasma membrane store-operated channels is crucial to Ca2+ signaling. Recently we found that IP3R interacts with the TRP3 Ca2+ channel on the plasma membrane and functional coupling of IP3R to TRP3 channel is important for store operated Ca2+ entry. Recently we found that IP3R is involved in determination of polarity and input specificity of activity-induced synaptic modification.