MTMR3 is a lipid phosphatase that catalyzes dephosphorylation of phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,5-bisphosphate, thereby regulating cellular signaling, membrane trafficking, and autophagy. Beyond its enzymatic activity, MTMR3 functions as a molecular adapter and regulates cytokinesis through midbody abscission. MTMR3 suppresses mTORC1 activity through direct interaction, with its phosphatase domain and N-terminal regions being critical for this function 1. The protein also controls autophagy flux by modulating PtdIns3P levels; in macrophages, MTMR3 decreases PRR-induced autophagy while increasing caspase-1 activation and inflammatory cytokine secretion 2. MTMR3 and its phosphoinositide product regulate cancer cell migration and invasion through Rac1 activation 3. Clinically, MTMR3 variants associate with multiple diseases. IgA nephropathy risk alleles enhance TLR9-induced IgA immunity through elevated MTMR3 expression 4. In primary open-angle glaucoma, MTMR3 variants demonstrate protective effects 5. Inflammatory bowel disease risk alleles increase MTMR3 expression, amplifying pattern recognition receptor signaling 2. In gastric cancer, MTMR3 suppression by miR-181a promotes proliferation and attenuates autophagy 6. Elevated MTMR3 associates with breast cancer risk in Egyptian populations 7, and common African ancestry variants in MTMR3 confer body mass index risk 8.