The phosphoinositide 5-phosphatase INPP5K: From gene structure to in vivo functions

Adv Biol Regul. 2021 Jan:79:100760. doi: 10.1016/j.jbior.2020.100760. Epub 2020 Oct 10.


INPP5K (Inositol Polyphosphate 5-Phosphatase K, or SKIP (for Skeletal muscle and Kidney enriched Inositol Phosphatase) is a member of the phosphoinositide 5-phosphatases family. Its protein structure is comprised of a N-terminal catalytic domain which hydrolyses both PtdIns(4,5)P2 and PtdIns(3,4,5)P3, followed by a SKICH domain at the C-terminus which is responsible for protein-protein interactions and subcellular localization of INPP5K. Strikingly, INPP5K is mostly concentrated in the endoplasmic reticulum, although it is also detected at the plasma membrane, in the cytosol and the nucleus. Recently, mutations in INPP5K have been detected in patients with a rare form of autosomal recessive congenital muscular dystrophy with cataract, short stature and intellectual disability. INPP5K functions extend from control of insulin signaling, endoplasmic reticulum stress response and structural integrity, myoblast differentiation, cytoskeleton organization, cell adhesion and migration, renal osmoregulation, to cancer. The goal of this review is thus to summarize and comment recent and less recent data in the literature on INPP5K, in particular on the structure, expression, intracellular localization, interactions and functions of this specific member of the 5-phosphatases family.

Keywords: 5-Phosphatase; Cataract; Congenital muscular dystrophy; Endoplasmic reticulum; Endoplasmic reticulum stress; INPP5K; Inositide; Insulin resistance; Insulin signaling; Intellectual disability; Phosphatidylinositol 3,4,5-trisphosphate; Phosphatidylinositol 4,5-bisphosphate; Phosphoinositide; SKIP; Unfolded protein response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Inositol Polyphosphate 5-Phosphatases / chemistry*
  • Inositol Polyphosphate 5-Phosphatases / genetics
  • Inositol Polyphosphate 5-Phosphatases / metabolism*
  • Mutation
  • Protein Domains
  • Protein Transport
  • Signal Transduction


  • Inositol Polyphosphate 5-Phosphatases