Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular Ca²⁺ release channels located on the endoplasmic reticulum (ER) and mediate Ca²⁺ mobilization from the ER to the cytoplasm in response to the binding of the second messenger, inositol 1,4,5-trisphosphate (IP₃)¹. IP₃-induced Ca²⁺ release is triggered by various external stimuli, and most non-excitable cells use this mechanism as the primary Ca²⁺ signaling pathway. IP3Rs are therefore thought to have important physiological roles in various cell types and tissues².

Three subtypes of IP3Rs, derived from three distinct genes, have been identified in mammals³. All three receptors have six transmembrane domains and a pore region between TM5 and TM6. The N-terminus as well as the C-terminus are cytoplasmic. Each IP3R consists of an N-terminal ligand binding domain (LBD) and a C-terminal domain which is linked by a long regulatory domain. The C-terminus is constitutively active, suggesting that the regulatory domain is required to maintain the suppression of channel activity⁴. 

Type 2 IP3R (IP3R2) is expressed in various tissues and cell lines. IP3R2 mRNA is localized in the intralobular duct cells of the submandibular gland, the urinary tubule cells of the kidney, the epithelial cells of epididymal ducts and the follicular granulosa cells of the ovary⁵. IP3R2 is active during osteoclast differentiation, and its absence causes a partial defect in osteoclastic differentiation.