While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum.

Considering that the average physiological pH is approximately 7.4, the main form of the phosphate groups bound to the inositol ring in vivo is PO42−.

Up until then phospholipids were believed to be inert structures only used by cells as building blocks for construction of the plasma membrane.

He hypothesized that receptor-activated hydrolysis of PIP2 produced a molecule that caused increases in intracellular calcium mobilization.

[6] This idea was researched extensively by Michell and his colleagues, who in 1981 were able to show that PIP2 is hydrolyzed into DAG and IP3 by a then unknown phosphodiesterase.

[7] Further research provided valuable information on the IP3 pathway, such as the discovery in 1986 that one of the many roles of the calcium released by IP3 is to work with DAG to activate protein kinase C (PKC).

[10] IP3's main functions are to mobilize Ca2+ from storage organelles and to regulate cell proliferation and other cellular reactions that require free calcium.

[14] The slow block to polyspermy in the sea urchin is mediated by the PIP2 secondary messenger system.

Huntington's disease occurs when the cytosolic protein Huntingtin (Htt) has an additional 35 glutamine residues added to its amino terminal region.

[15] Alzheimer's disease involves the progressive degeneration of the brain, severely impacting mental faculties.

All of the mutated forms of these genes observed to date have been found to cause abnormal Ca2+ signaling in the ER.

Calcium channel blockers have been used to treat Alzheimer's disease with some success, and the use of lithium to decrease IP3 turnover has also been suggested as a possible method of treatment.