Inactivation of the tumor suppressor lipid phosphatase INPP4B is common in triple-negative breast cancer (TNBC). We generated a genetically engineered TNBC mouse model deficient in . We found a dose-dependent increase in tumor incidence in homozygous and heterozygous knockout mice compared with wild-type (WT), supporting a role for as a tumor suppressor in TNBC. Tumors derived from knockout mice are enriched for AKT and MEK gene signatures. Consequently, mice with deficiency are more sensitive to PI3K or MEK inhibitors compared with WT mice. Mechanistically, we found that deficiency increases PI(3,4)P levels in endocytic vesicles but not at the plasma membrane. Moreover, loss delays degradation of EGFR and MET, while promoting recycling of receptor tyrosine kinases (RTK), thus enhancing the duration and amplitude of signaling output upon growth factor stimulation. Therefore, inactivation in TNBC promotes tumorigenesis by modulating RTK recycling and signaling duration. SIGNIFICANCE: Inactivation of the lipid phosphatase is frequent in TNBC. Using a genetically engineered mouse model, we show that INPP4B functions as a tumor suppressor in TNBC. INPP4B regulates RTK trafficking and degradation, such that loss of INPP4B prolongs both PI3K and ERK activation..