Inositol monophosphatase (IMPase) (IMPase)

Inositol monophosphatase (IMPase) is a key enzyme in the phosphoinositide signaling pathway, responsible for dephosphorylating inositol monophosphates to generate free myo-inositol [UniProt: P29218]. This recycling process is essential for the resynthesis of phosphatidylinositol-4,5-bisphosphate (PIP2), a precursor for secondary messengers like inositol trisphosphate (IP3) and diacylglycerol (DAG) [PubMed: 15173104]. IMPase is the primary molecular target of lithium, the gold-standard treatment for bipolar disorder [StatPearls: Lithium]. By inhibiting IMPase uncompetitively, lithium reduces the pool of available inositol, thereby selectively dampening overactive signaling in the brain—a mechanism known as the "inositol depletion hypothesis" [PubMed: 18432327]. Beyond bipolar disorder, IMPase is investigated for its roles in other neuropsychiatric conditions and neurodegenerative diseases like Alzheimer's [PubMed: 23533133]. Dysregulation of this pathway is linked to altered neuronal excitability and synaptic plasticity. Therapeutic targeting of this enzyme aims to modulate neuronal excitability without affecting basal cellular functions.

Other names

Myo-inositol monophosphataseIMPA1IMPA2Inositol-1-phosphataseInositol-1(or 4)-monophosphatase

Uncompetitive inhibition of the enzyme, preventing the recycling of inositol and leading to the depletion of intracellular myo-inositol levels, which dampens overactive phosphoinositide signaling [PubMed: 18432327].