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The inositol 1,4,5 trisphosphate (IP3 ) receptor (IP3 R) is a Ca 2+ release channel that responds to the second messenger IP3 . Exquisite modulation of intracellular Ca 2+ release via IP3 Rs is achieved by the ability of IP3 R to integrate signals from numerous small molecules and proteins including nucleotides, kinases, and phosphatases, as well as nonenzyme proteins. Because the ion conduction pore composes only ∼5% of the IP3 R, the great bulk of this large protein contains recognition sites for these substances. Through these regulatory mechanisms, IP3 R modulates diverse cellular functions, which include, but are not limited to, contraction/ excitation, secretion, gene expression, and cellular growth. We review the unique properties of the IP3 R that facilitate cell-type and stimulus-dependent control of function, with special emphasis on protein-binding partners. [ABSTRACT FROM AUTHOR]