In a variety of cells, the Ca²⁺ signalling process is mediated by the endoplasmic-reticulum-membrane-associated Ca²⁺ release channel, inositol 1,4,5-trisphosphate (InsP₃) receptor (InsP₃R). Being ubiquitous and present in organisms ranging from humans to Caenorhabditis elegans, InsP₃R has a vital role in the control of cellular and physiological processes as diverse as cell division, cell proliferation, apoptosis, fertilization, development, behaviour, memory and learning. Mouse type I InsP₃R (InsP₃R1), found in high abundance in cerebellar Purkinje cells, is a polypeptide with three major functionally distinct regions: the amino-terminal InsP₃-binding region, the central modulatory region and the carboxy-terminal channel region. Here we present a 2.2-Å crystal structure of the InsP₃-binding core of mouse InsP₃R1 in complex with InsP₃. The asymmetric, boomerang-like structure consists of an N-terminal β-trefoil domain and a C-terminal α-helical domain containing an ‘armadillo repeat’-like fold. The cleft formed by the two domains exposes a cluster of arginine and lysine residues that coordinate the three phosphoryl groups of InsP₃. Putative Ca²⁺-binding sites are identified in two separate locations within the InsP₃-binding core.