Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase

PIP4P1 encodes Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase, a 277-amino-acid enzyme that catalyzes hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P) (UniProt: Q86T03). Beyond lipid phosphate metabolism, the protein regulates lysosomal positioning by recruiting JIP4 to lysosomal membranes and promotes retrograde lysosomal transport. It also contributes to V-ATPase assembly in lysosomal lipid rafts, supporting amino acid-dependent mTORC1 activation and potentially influencing cellular cholesterol metabolism.

In Alzheimer's Disease, PIP4P1 shows reduced expression in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Analysis of human post-mortem AD brain by TMT-labeled proteomics across four subcellular fractions (P2, P3, S2, S3) revealed a mean log2 fold-change of −0.3165, indicating consistent downregulation. This decreased expression may impair lysosomal function and nutrient sensing pathways implicated in neurodegeneration, though the functional consequences in AD pathology remain to be clarified.