MTMR8 (myotubularin related protein 8) is a lipid phosphatase located on chromosome X that catalyzes dephosphorylation of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P₂) at the D-3 position 1. The protein contains a conserved phosphatase domain and localizes to the cytoplasm, nuclear envelope, and intermediate compartment-Golgi regions 2. Functionally, MTMR8 operates as a catalytically active component of the myotubularin protein family, with enhanced enzymatic activity when complexed with the inactive binding partner MTMR9 1. The MTMR8/MTMR9 complex negatively regulates macroautophagy by dephosphorylating PtdIns(3)P, thereby reducing autophagic flux and preventing autophagic vesicle accumulation 31. Beyond autophagy, MTMR8 cooperates with phosphoinositide 3-kinase (PI3K) to regulate actin filament organization and muscle development 4. MTMR8 also participates in ER-to-Golgi trafficking through recruitment by MTMR9 and regulation of the RAB1A GTPase, affecting protein secretion including the WNT3A pathway 2. Disease relevance includes associations with multiple sclerosis susceptibility, where MTMR8 variants are identified among X-linked genetic risk factors affecting immunity and remyelination pathways 5.