MTMR2 is a lipid phosphatase that catalyzes dephosphorylation of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate at the D-3 position 12. This enzymatic activity regulates phosphoinositide levels critical for autophagy initiation and autophagosome maturation 3. MTMR2 functions as a negative regulator of autophagy; its selective degradation during mitochondrial stress enhances autophagosome biogenesis and mitophagy, promoting mitochondrial quality control in neurons 4. Loss-of-function mutations in MTMR2 cause autosomal recessive Charcot-Marie-Tooth disease type 4B1, a demyelinating peripheral neuropathy affecting endosomal membrane trafficking 56. Notably, MTMR2 exhibits tissue-specific enrichment in the peripheral nervous system during development 5. Beyond its genetic association with CMT4B, MTMR2 is aberrantly upregulated in multiple cancer types including hepatocellular carcinoma, NK/T cell lymphoma, and gastric cancer, where elevated expression correlates with poor prognosis and metastatic potential 789. Therapeutically, MTMR2 expression ameliorates myotubular myopathy caused by MTM1 mutations, suggesting potential for compensatory protein therapy in myopathies 10.