Binding of inositol 1,4,5-trisphosphate (IP₃) to the amino-terminal region of IP₃ receptor promotes Ca²⁺ release from the endoplasmic reticulum. Within the amino terminus, the first 220 residues directly preceding the IP₃ binding core domain play a key role in IP₃ binding suppression and regulatory protein interaction. Here we present a crystal structure of the suppressor domain of the mouse type 1 IP₃ receptor at 1.8 Å. Displaying a shape akin to a hammer, the suppressor region contains a Head subdomain forming the β-trefoil fold and an Arm subdomain possessing a helix-turn-helix structure. The conserved region on the Head subdomain appeared to interact with the IP₃ binding core domain and is in close proximity to the previously proposed binding sites of Homer, RACK1, calmodulin, and CaBP1. The present study sheds light onto the mechanism underlying the receptor's sensitivity to the ligand and its communication with cellular signaling proteins.