Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma

Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (PIP4K2C) is a lipid kinase that phosphorylates phosphatidylinositol 5-phosphate to generate phosphatidylinositol 4,5-bisphosphate (UniProt: Q8TBX8). The enzyme exhibits low intrinsic activity and preferentially uses GTP over ATP as a phosphate donor. PIP4K2C negatively regulates insulin signaling through a catalytic-independent mechanism by interacting with and suppressing PIP5K-mediated synthesis of phosphatidylinositol lipids, thereby reducing insulin-dependent phosphoinositide conversions (UniProt: Q8TBX8).

PIP4K2C participates in phosphoinositide metabolism, a critical signaling pathway in neurons and peripheral tissues. The protein is implicated in metabolic regulation through its interaction with insulin signaling networks.

In Alzheimer's Disease, PIP4K2C is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.62. This downregulation was observed across one subcellular fraction in a quantitative proteomics study of AD brain samples, suggesting potential dysregulation of phosphoinositide-dependent signaling in AD pathology.