Inositol polyphosphate-4-phosphatase type I A

INPP4A (inositol polyphosphate-4-phosphatase type I A) is a phosphatase that hydrolyzes the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate and related inositol phosphates (UniProt: Q96PE3). It antagonizes PI3K-AKT/PKB signaling by dephosphorylating phosphoinositides, thereby modulating cell cycle progression and cell survival. The protein may also protect neurons from excitotoxic death by regulating synaptic localization of N-methyl-D-aspartate-type glutamate receptors and NMDAR-mediated signaling (UniProt: Q96PE3).

INPP4A is broadly expressed across tissues and participates in phosphoinositide metabolism and glutamatergic neurotransmission, functions central to neuronal homeostasis. No disease associations are documented in UniProt curated entries.

In Alzheimer's Disease, INPP4A is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −1.22) based on quantitative proteomics of subcellular fractions (Chaparral AD proteomics). This decreased abundance suggests potential dysregulation of phosphoinositide signaling and neuroprotective mechanisms in AD pathology, warranting further investigation into its role in disease progression.