Inositol polyphosphate 4-phosphatase type II (INPP4B)

Inositol polyphosphate 4-phosphatase type II (INPP4B) is an enzyme that removes the phosphate group from the 4-position of inositol 3,4-bisphosphate, playing a key role in the regulation and homeostasis of phosphoinositides in cells[1][2][5]. It is especially critical in the hydrolysis of phosphatidylinositol 3,4-bisphosphate (PI(3,4)P₂), converting it to phosphatidylinositol 3-phosphate (PI(3)P), and thus regulates the PI3K/Akt signaling pathway, which is crucial for cell proliferation, survival, and motility[1][2][3]. INPP4B contains a C2 lipid-binding domain, a NHR2 domain implicated in protein-protein interactions, and a C-terminal phosphatase domain with activity towards inositol polyphosphates[1][2]. Loss of INPP4B function, mutation, or downregulation is frequently observed in prostate and breast cancers, where it acts as a tumor suppressor by restricting Akt phosphorylation and subsequent cell proliferation[1][2][3][4]. Its loss is particularly associated with aggressive forms of cancer and poorer prognosis[3][1]. No approved drugs are currently known to modulate INPP4B directly, nor are there defined safety challenges for INPP4B-targeted therapeutics; however, loss of INPP4B function in cancer presents a substantial clinical challenge[1][3].

Other names

Inositol polyphosphate-4-phosphatase type II BInositol polyphosphate 4-phosphatase IIType II inositol 3,4-bisphosphate 4-phosphatase4-phosphatase IIINPP4Binositol polyphosphate-4-phosphatase, type II