Phosphatidylinositol 5-phosphate 4-kinase type-2 beta

Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (PIP4K2B) is a lipid kinase that catalyzes the biosynthesis of phosphatidylinositol 4,5-bisphosphate (PIP2), a critical signaling phospholipid. The protein exhibits GTP-sensing activity, preferentially using GTP rather than ATP for its enzymatic function, and this GTP-sensitivity is integral to metabolic adaptation (UniProt: P78356). PIP4K2B also negatively regulates insulin signaling through interaction with PIP5K proteins, suppressing PIP5K-mediated PIP2 synthesis and subsequent conversion to PIP3.

In Alzheimer's disease, PIP4K2B is downregulated in post-mortem AD brain tissue relative to age-matched controls (Chaparral AD proteomics). Quantitative proteomics using TMT labeling across four subcellular fractions revealed a mean log2 fold-change of −0.88 (ad:direction:down), suggesting reduced expression of this lipid kinase in the AD brain. Given its role in PIP2 biosynthesis and metabolic signaling, this reduction may reflect altered phosphoinositide metabolism in neurodegeneration, though the functional consequence remains to be elucidated.