Inositol polyphosphate 5-phosphatase K (INPP5K)

Inositol polyphosphate 5-phosphatase K (INPP5K) is an enzyme that catalyzes the hydrolysis of the 5-phosphate from phosphoinositides such as phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate[3][4]. It is primarily localized to the endoplasmic reticulum but is also found at the plasma membrane, cytosol, and nucleus[3][4]. INPP5K is involved in diverse cellular functions, including the regulation of insulin and IGF-II signaling, endoplasmic reticulum stress response and architecture, cytoskeleton dynamics, myoblast differentiation, and immune cell signaling—especially through modulation of IL-7 receptor-mediated processes[1][2][3][4]. Mutations in INPP5K are linked to autosomal recessive congenital muscular dystrophy with associated cataracts, cognitive deficits, and short stature[3][4]. It acts as a brake on PI3K/AKT/mTOR autocrine loops, modulates cytoskeletal organization, connects the ER to microtubules, and controls signaling pathways relevant to muscle, kidney, and immune system development and disorders[1][2][3][4].

Other names

Skeletal muscle and kidney-enriched inositol phosphataseSKIPPPSMDCCAIDPhosphatidylinositol-3,4,5-trisphosphate 5-phosphatasePhosphatidylinositol-4,5-bisphosphate 5-phosphataseInositol polyphosphate-5-phosphatase K

Enzyme inhibition or modulation of INPP5K affects downstream phosphoinositide-dependent signaling, including PI3K/AKT/mTOR and IL-7R signaling pathways[1][3][4].