Phosphatase that acts on lipids with a phosphoinositol headgroup (PubMed:19038970, PubMed:22647598). Dephosphorylates phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,5-bisphosphate (PubMed:19038970, PubMed:22647598) (Probable). Binds with high affinity to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) but also to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P), phosphatidic acid and phosphatidylserine (PubMed:19038970). Negatively regulates ER-Golgi protein transport (By similarity). Probably in association with MTMR9, plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3-phosphate in membrane ruffles (PubMed:24591580). Acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4(+) T-cells possibly by decreasing intracellular levels of phosphatidylinositol 3-phosphate (PubMed:15831468). Negatively regulates proliferation of reactivated CD4(+) T-cells (PubMed:16847315). In complex with MTMR9, negatively regulates DNA damage-induced apoptosis (PubMed:19038970, PubMed:22647598). The formation of the MTMR6-MTMR9 complex stabilizes both MTMR6 and MTMR9 protein levels (PubMed:19038970). a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + phosphate a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + phosphate 1,2-dioctanoyl-sn-glycero-3-phospho-(1-D-myo-inositol-3-phosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate Allosterically activated by phosphatidylserine and/or phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:19038970). Interaction with MTMR9 increases catalytic activity towards phosphatidylinositol 3,5-bisphosphate (PubMed:19038970). Optimum pH is 7. Homodimer (PubMed:19038970). Heterodimer (via C-terminus) with MTMR9 (via C-terminus) (PubMed:12890864, PubMed:16787938, PubMed:19038970, PubMed:23188820). Interacts with ALKBH4 (PubMed:23145062). Interacts with KCNN4 (PubMed:15831468). Interacts (via GRAM domain) with RAB1B (in GDP-bound form); the interaction regulates MTMR6 recruitment to the endoplasmic reticulum-Golgi intermediate compartment (PubMed:23188820). Localizes to ruffles during EGF-induced macropinocytosis (By similarity). Colocalizes with MTMR9 to the perinuclear region (PubMed:19038970). Partially localizes to the endoplasmic reticulum (PubMed:19038970). Co-localizes with RAB1B to the endoplasmic reticulum-Golgi intermediate compartment and to the peri-Golgi region (By similarity). Expressed in CD4+ T-cells. The GRAM domain is required for cell membrane localization. The C-terminus domain (aa 502-621) mediates interaction with MTMR9. Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.