The IP 3 R [IP 3 (inositol 1,4,5-trisphosphate) receptor] is responsible for Ca 2+ release from the ER (endoplasmic reticulum). We have been working extensively on the P 400 protein, which is deficient in Purkinje-neuron-degenerating mutant mice. We have discovered that P 400 is an IP 3 R and we have determined the primary sequence. Purified IP 3 R, when incorporated into a lipid bilayer, works as a Ca 2+ release channel and overexpression of IP 3 R shows enhanced IP 3 binding and channel activity. Addition of an antibody blocks Ca 2+ oscillations indicating that IP 3 R1 works as a Ca 2+ oscillator. Studies on the role of IP 3 R during development show that IP 3 R is involved in fertilization and is essential for determination of dorso-ventral axis formation. We found that IP 3 R is involved in neuronal plasticity. A double homozygous mutant of IP 3 R2 (IP 3 R type 2) and IP 3 R3 (IP 3 R type 3) shows a deficit of saliva secretion and gastric juice secretion suggesting that IP 3 Rs are essential for exocrine secretion. IP 3 R has various unique properties: cryo-EM (electron microscopy) studies show that IP 3 R contains multiple cavities; IP 3 R allosterically and dynamically changes its form reversibly (square form–windmill form); IP 3 R is functional even though it is fragmented by proteases into several pieces; the ER forms a meshwork but also forms vesicular ER and moves along microtubules using a kinesin motor; X ray analysis of the crystal structure of the IP 3 binding core consists of an N-terminal β-trefoil domain and a C-terminal α-helical domain. We have discovered ERp44 as a redox sensor in the ER which binds to the luminal part of IP 3 R1 and regulates its activity. We have also found the role of IP 3 is not only to release Ca 2+ but also to release IRBIT which binds to the IP 3 binding core of IP 3 R.