Inositol polyphosphate 1-phosphatase

Inositol polyphosphate 1-phosphatase (INPP1) is a magnesium-dependent phosphatase that catalyzes hydrolysis of the 1-position phosphate from inositol 1,4-bisphosphate and inositol 1,3,4-trisphosphate, thereby participating in inositol phosphate metabolism (UniProt: P49441). This metabolic pathway regulates intracellular signaling through the phosphoinositide cascade, which controls calcium mobilization and various downstream cellular functions.

INPP1 is expressed in human tissues and its phosphatase activity is central to terminating inositol phosphate signaling cascades. No disease associations are currently annotated in the UniProt entry (UniProt: P49441); however, the protein has been identified as relevant to Alzheimer's disease pathology through proteomic analysis.

In Alzheimer's disease, INPP1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.81 (Chaparral AD proteomics). This upregulation was detected via TMT-labeled quantitative proteomics across multiple subcellular fractions, suggesting that altered inositol phosphate metabolism may be associated with AD pathology. The functional implications of elevated INPP1 activity in AD neurodegeneration warrant further investigation.