Several X-ray crystallographic  and electron cryomicroscopic (cryo-EM)  structures of IPRs from mouse, rat, and human have defined the overall architecture of the channel. The 1.2 MDa C4-symmetric assembly consists of an ER-embedded transmembrane domain (TMD) in a domain-swapped 6 transmembrane (6TM) cation channel fold that is capped by a large cytosolic domain (CD). In this manner, IPRs share significant homology with the much larger and distantly-related RyRs. The CD contains all known ligand binding sites, including the IP binding site, two Ca binding sites, an adenine nucleotide binding site, and a CH Zn finger fold. A comprehensive Ca-dependent conformational landscape has recently been defined by cryo-EM.