INPP4B (inositol polyphosphate-4-phosphatase type II B) is a lipid phosphatase that catalyzes hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate and inositol 1,3,4-trisphosphate 12. The enzyme plays a role in late-stage macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles 2. INPP4B antagonizes PI3K-AKT/PKB signaling by dephosphorylating phosphoinositides, thereby modulating cell cycle progression and survival 31. INPP4B exhibits paradoxical dual roles in cancer. In hepatocellular carcinoma, prostate cancer, and endometrial cancer, INPP4B overexpression suppresses cell proliferation, migration, invasion, and chemoresistance through PI3K/AKT inhibition 456. However, in pancreatic ductal adenocarcinoma (PDAC), INPP4B overexpression promotes aggressiveness by driving PtdIns(3,5)P2 generation on lysosomes via PIKfyve, triggering TRPML-1-mediated calcium release and enhancing migratory and invasive properties 7. This context-dependent behavior reflects differential mechanisms: tumor-suppressive function primarily involves PI3K/AKT inhibition, while oncogenic function may involve SGK3 signaling and lysosomal exocytosis modulation 8. Clinically, reduced INPP4B expression correlates with advanced tumor stage and poor prognosis in multiple cancers, suggesting therapeutic potential as a tumor suppressor target.