Myotubularin-related protein 14 (MTMR14) (MTMR14)

Myotubularin-related protein 14 (MTMR14), also known as JUMPY or Egg-derived tyrosine phosphatase (EDTP), is a lipid phosphatase that serves as a key negative regulator of autophagy [NIH, 2019]. It acts by dephosphorylating phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), signaling lipids that are essential for the nucleation and maturation of autophagosomes [FlyBase, 2026]. In humans, loss-of-function mutations in MTMR14 are associated with centronuclear myopathy, a condition characterized by muscle weakness and fatigue [UniProt, Q86WU2]. Conversely, the accumulation of MTMR14 with age has been linked to declining autophagic capacity in neurons, contributing to the progression of neurodegenerative diseases such as Alzheimer's and Huntington's [Neuroscience Letters, 2019]. Pharmacological inhibitors like AUTEN-67 target MTMR14 to enhance autophagic flux, promoting the clearance of toxic protein aggregates and offering a potential therapeutic strategy for age-related and proteinopathic disorders [Autophagy, 2016].

Other names

JUMPYEgg-derived tyrosine phosphataseEDTPPhosphatidylinositol-3-phosphate phosphatasePTP-EDTP

Inhibition of the lipid phosphatase activity of MTMR14/EDTP, which prevents the dephosphorylation of phosphatidylinositol 3-phosphate (PtdIns3P), thereby increasing PtdIns3P levels and promoting the initiation of autophagy and autophagosome formation.