Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha

PIP4K2A (phosphatidylinositol 5-phosphate 4-kinase type-2 alpha) is a serine/threonine kinase that catalyzes the phosphorylation of phosphatidylinositol 5-phosphate to form phosphatidylinositol 4,5-bisphosphate, a key signaling lipid (UniProt: P48426). The enzyme possesses both ATP- and GTP-dependent kinase activities and regulates cellular PtdIns5P pools in response to tyrosine phosphorylation. PIP4K2A functions in multiple cellular processes including autophagy, lysosome-peroxisome membrane contacts, cholesterol transport, and insulin signaling suppression.

PIP4K2A plays critical roles in intracellular lipid metabolism and autophagosome-lysosome fusion, with functional relevance across cytosolic and nuclear compartments. The protein negatively regulates insulin signaling through a catalytic-independent mechanism and collaborates with PIP4K2B during nutrient stress responses (UniProt: P48426). No specific non-AD disease associations are documented in UniProt.

In Alzheimer's disease, PIP4K2A is significantly down-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC: −0.36; Chaparral AD proteomics). This down-regulation, observed via TMT-labeled DDA proteomics across multiple subcellular fractions, suggests diminished phosphoinositide signaling capacity and potentially impaired autophagy and lipid metabolism in the AD brain.