Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR14

MTMR14 is a lipid phosphatase that catalyzes dephosphorylation of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, converting them to phosphatidylinositol and phosphatidylinositol 5-phosphate respectively (UniProt: Q8NCE2). These lipid signaling molecules regulate membrane trafficking and autophagy processes in cells. In UniProt, MTMR14 is associated with centronuclear myopathy 1 (CNM1), a congenital muscle disorder characterized by progressive muscular weakness and centrally located muscle fiber nuclei.

In Alzheimer's Disease brain tissue, MTMR14 is significantly down-regulated compared to age-matched controls (mean log2FC: −0.4286) in post-mortem human brain analyzed by quantitative proteomics across multiple subcellular fractions (Chaparral AD proteomics). This reduction in a lipid phosphatase involved in endosomal and autophagosomal signaling may reflect dysregulation of membrane trafficking and lysosomal pathways implicated in amyloid and tau pathology accumulation. The functional consequence of MTMR14 loss in AD pathogenesis remains to be clarified, though impaired phosphoinositide signaling could contribute to proteostatic dysfunction.