MTMR4 is a lipid phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate, converting them to phosphatidylinositol and phosphatidylinositol 5-phosphate 1. This activity negatively regulates endocytic recycling, endosomal trafficking, and lysosomal maturation by reducing PI3P levels on endosomal membranes 1. MTMR4 dynamically localizes to phagosomes and regulates their maturation by controlling PI3P degradation; MTMR4 overexpression inhibits FcγR-mediated phagocytosis, while knockdown enhances phagosomal maturation and bacterial degradation 2. In innate immunity, MTMR4 suppresses DNA-mediated immune responses by modulating PI3P-dependent STING trafficking in endosomal compartments 3. Beyond lipid phosphatase activity, MTMR4 functions as a molecular adapter regulating mitotic cytokinesis and negatively modulates BMP/Smad signaling through R-Smad dephosphorylation 4. Recently, RAF1 kinase phosphorylation of MTMR4 at autolysosomes was identified as critical for autophagic lysosome reformation and autophagy regulation 5. Clinically, MTMR4 polymorphisms associate with plasma cholesterol levels, and altered MTMR4 expression correlates with thoracic aortic aneurysm and atherosclerosis pathology 67.