Inositol 1,4,5-trisphosphate receptor (IP3R) (IP3R)

The Inositol 1,4,5-trisphosphate receptor (IP3R) is a family of large, tetrameric ligand-gated calcium channels primarily localized to the endoplasmic reticulum (ER) membrane (UniProt, 2023). These receptors are essential for intracellular calcium signaling, as they release Ca2+ from internal stores into the cytoplasm in response to the second messenger IP3, which is produced by phospholipase C (PLC) activation (Mikoshiba, 2007). The family comprises three main isoforms—IP3R1, IP3R2, and IP3R3—which exhibit different affinities for IP3 and are regulated by various factors including cytosolic calcium, ATP, and phosphorylation (Prole & Taylor, 2019). IP3Rs are involved in a vast array of physiological processes, ranging from muscle contraction and neurotransmission to cell division and apoptosis (PubMed, 2022). Dysregulation of these receptors is linked to numerous diseases, such as spinocerebellar ataxia type 15/16 (ITPR1 mutations) and various malignancies where IP3R-mediated calcium transfer to mitochondria influences cell survival (StatPearls, 2023). Although several small molecules like Xestospongin C and 2-APB are used in research to modulate IP3R activity, the development of clinical therapeutics remains challenging due to the receptors' ubiquitous expression and the risk of disrupting fundamental cellular calcium homeostasis (Alzayady et al., 2016).

Other names

IP3 receptorInsP3RITPRInositol trisphosphate receptorInositol 1,4,5-triphosphate receptor

The IP3 receptor family functions as ligand-gated calcium channels that release calcium ions from the endoplasmic reticulum into the cytosol upon binding of the second messenger inositol 1,4,5-trisphosphate (IP3) (Mikoshiba, 2007; UniProt, 2023).