PIP4P2 (encoding TMEM55A) is a phosphatidylinositol-4,5-bisphosphate 4-phosphatase that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P) and phosphatidylinositol-5-phosphate (PI5P) 1. The enzyme exhibits strict substrate specificity, with no activity toward phosphatidylinositol 3,4,5-trisphosphate or other inositol phosphates. PIP4P2 positively regulates basal autophagy through its phosphatase activity 2. In alpha cells, TMEM55A regulates glucagon secretion by controlling intracellular PI5P levels and modulating cortical F-actin remodeling in response to oxidative stress, independent of calcium channel activity 1. Clinically, PIP4P2 shows prognostic significance in cancer. High PIP4P2 expression in gastric cancer tissue correlates with poor prognosis and reduced immunotherapy efficacy through PI3K/AKT pathway activation 3. In hepatocellular carcinoma, PIP4P2 is part of a 3-gene prognostic signature associated with microbiome-driven tumor heterogeneity and immune microenvironment composition 4. These findings establish PIP4P2 as a multifunctional lipid phosphatase with important roles in cellular metabolism, exocytosis, autophagy regulation, and cancer progression.