Phospholysine phosphohistidine inorganic pyrophosphate phosphatase

LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) is a 270-amino-acid phosphatase that catalyzes hydrolysis of imidodiphosphate, 3-phosphohistidine, and 6-phospholysine, with broader activity toward inorganic diphosphate, though with lower efficiency (UniProt: Q9H008).

The protein is present in human tissues and localizes to multiple subcellular compartments. No primary disease associations are documented in the UniProt record, though the gene has been flagged for Alzheimer's Disease relevance in curated datasets.

LHPP is upregulated in Alzheimer's Disease brain tissue. In post-mortem AD brain samples compared to age-matched controls analyzed via TMT-labeled quantitative proteomics across four subcellular fractions (P2, P3, S2, S3), LHPP showed a mean log2 fold-change of +0.62, indicating elevated expression in AD pathology (Chaparral AD proteomics). The functional role of this phosphatase upregulation in neurodegeneration remains to be elucidated.