Target intelligence / Profile preview

Inositol polyphosphate-5-phosphatase A (INPP5A)

Target: INPP5A
Molecular classification: Enzyme, Phosphatase, Membrane-associated protein

Overview

Inositol polyphosphate-5-phosphatase A (INPP5A) is a membrane-associated phosphatase that catalyzes the dephosphorylation of inositol 1,4,5-trisphosphate (IP3) to inositol 1,4-bisphosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate. This activity regulates intracellular calcium mobilization by controlling IP3 levels, a key second messenger in many signaling pathways. INPP5A is essential for the survival of certain neuronal populations and is selectively required for the viability of GNAQ/11-mutant uveal melanoma cells, making it a potential cancer therapeutic target. Genetic deficiency or dysfunction is associated with spinocerebellar ataxia and neurodegenerative disease risk. No approved drugs directly target INPP5A and any therapeutic inhibition would require careful monitoring for potential neurological side effects due to its role in the central nervous system.

Other names: Type I inositol 1,4,5-trisphosphate 5-phosphatase5PTASE43 kDa inositol polyphosphate 5-phosphataseInositol polyphosphate-5-phosphatase, 40kDaInositol polyphosphate-5-phosphatase, 40kD

Mechanism of action

Inhibition of INPP5A synthetic-lethal in GNAQ/11-mutant uveal melanoma (preclinical)

Biological functions

Signal transductionCalcium signaling regulationRegulation of intracellular second messenger levelsSurvival of cerebellar Purkinje cells

Disease associations

CancerNeurodegenerative diseaseSpinocerebellar ataxia

Safety considerations

Potential risk of neurotoxicity (due to vital role in cerebellar Purkinje cell survival)

Biomarkers

Inositol tetrakisphosphate (IP4, predictive for INPP5A dependency in GNAQ/11-mutant cancers)

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