Inositol 1,4,5-trisphosphate 3-kinase B (ITPKB)

Inositol 1,4,5-trisphosphate 3-kinase B (ITPKB) is an enzyme and member of the inositol 1,4,5-trisphosphate 3-kinase family that phosphorylates inositol 1,4,5-trisphosphate (IP3) to generate inositol 1,3,4,5-tetrakisphosphate (IP4), thereby playing a pivotal role in modulating intracellular calcium signaling and downstream cellular processes. ITPKB activity is subject to regulation by calcium/calmodulin and protein phosphorylation, and it is critical for cellular signal transduction, cell proliferation, apoptosis, hematopoietic stem cell maintenance, and immune cell survival. Genome-wide studies have linked variants in ITPKB with reduced risk of sporadic Parkinson’s disease, with functional data indicating that it acts as a negative regulator of α-synuclein aggregation through controlling calcium flux between the endoplasmic reticulum and mitochondria. Dysregulation of ITPKB is implicated in neurodegenerative disorders, immune dysfunction, and certain cancers, making it a molecule of interest both for basic research and therapeutics

Other names

Inositol-trisphosphate 3-kinase BIP3 3-kinase BIP3K BInsP 3-kinase BIP3KBIP3-3KBIP3KIP3K-BPIG37Inositol 1,4,5-trisphosphate 3-kinase Bproliferation-inducing protein 37

Inhibition of ITPKB blocks phosphorylation of IP3 to IP4, prolonging IP3 signaling, increasing ER calcium release and downstream effects (altering mitochondrial respiration, autophagy, and cell survival). Pharmacological inhibition increases α-synuclein aggregation in neurons; overexpression diminishes it