Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2)

Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) is an intracellular ligand-gated calcium channel predominantly localized to the endoplasmic reticulum. It mediates the release of calcium into the cytosol in response to inositol 1,4,5-trisphosphate (IP3), a second messenger generated downstream of many cell surface receptors[1][7]. ITPR2 is one of three IP3 receptor isoforms, characterized by high affinity for IP3, and is especially enriched in organs such as the heart, liver, and cells involved in myelination and neural signaling[4]. The channel plays a critical role in cellular processes requiring calcium signaling, including cell migration, division, apoptosis, muscle contraction, and neuronal activity. Dysfunction or mutation of ITPR2 is linked to disease states such as isolated anhidrosis and psychiatric disorders involving myelin abnormalities[1][2]. Recent studies also implicate ITPR2 in cellular aging, where its loss reduces calcium flux between ER and mitochondria and lessens senescence[5]. Direct drug targeting of ITPR2 is limited due to broad systemic requirements for IP3-mediated calcium signaling, but manipulation of related pathways is under exploration for certain conditions.

Other names

IP3R2InsP3R2IP3R 2Type 2 InsP3 receptorInositol 1,4,5-trisphosphate-gated calcium channel ITPR2CFAP48IP3 receptor isoform 2Cilia and flagella associated protein 48ANHDINSP3R2

Drugs or agents that modulate GPCR-induced IP3 production can indirectly regulate ITPR2 activity. Antagonists of compensatory calcium channels (TRPC6, mGluR5) can modulate calcium homeostasis in cells lacking ITPR2[2]. Cellular signaling molecules that alter ER calcium release via IP3R2 response to IP3.