Inositol polyphosphate 1-phosphatase (INPP1)

Inositol polyphosphate 1-phosphatase (INPP1) is a magnesium-dependent, lithium-inhibited phosphatase enzyme that catalyzes the removal of the phosphate group at the 1-position of the inositol ring from inositol 1,4-bisphosphate and inositol 1,3,4-trisphosphate. It is a key component of the inositol phosphate signaling and phosphatidylinositol signaling pathways. INPP1 activity is relevant for neuronal signaling and is potently inhibited by therapeutic concentrations of lithium, which is used in the treatment of bipolar disorder and other neurological diseases. The enzyme is a prototype member of the metal-dependent phosphomonoesterase family, defined by a conserved structural core and a motif that mediates substrate and metal (Mg2+, Li+) binding. Structural studies reveal that lithium exerts its inhibitory effect by binding to a specific site within the catalytic center, disrupting enzymatic hydrolysis. While INPP1 itself is not a direct drug target outside of lithium therapy, its functional and inhibitory relationship to lithium is of notable clinical relevance[1][3][4].

Other names

inositol polyphosphate-1-phosphataseINPP1inositol-1,4-bisphosphate 1-phosphataseinositol-1,3,4-trisphosphate 1-phosphatase

Uncompetitive inhibition (by lithium) of enzyme activity via lithium binding to an active site metal-binding motif, interfering with catalysis[1][3]