Inositol monophosphatase 1

Summary

Inositol monophosphatase 1 (IMPA1, also known as IMP1 or IMPase 1) is a phosphatase that catalyzes the dephosphorylation of myo-inositol monophosphates to generate free myo-inositol, and also acts on several other inositol phosphates and sugar-phosphates in vitro (UniProt: P29218). The enzyme is essential for provision of inositol needed for phosphatidylinositol and polyphosphoinositide synthesis, supporting normal brain function. IMPA1 is recognized as the pharmacological target of lithium in the brain, which has therapeutic application in bipolar disorder (UniProt: P29218).

A rare autosomal recessive form of intellectual developmental disorder (MRT59, MIM 617323) is associated with IMPA1 mutations (UniProt: P29218), underscoring its role in neurological function. In Alzheimer's disease, IMPA1 protein levels are significantly downregulated in post-mortem AD brain relative to age-matched controls (mean log2FC −0.23; Chaparral AD proteomics), based on quantitative proteomics across multiple subcellular fractions. This reduction may relate to impaired inositol metabolism and phosphoinositide signaling in AD pathology.