INPP5F (inositol polyphosphate-5-phosphatase F) is a phosphoinositide phosphatase that primarily functions in endocytic membrane trafficking by catalyzing the hydrolysis of phosphatidylinositol 4-phosphate (PtdIns(4)P) 1. The protein localizes to endocytic compartments including clathrin-coated vesicles, macropinosomes, and Rab5 endosomes, where it cooperates with OCRL in sequential dephosphorylation of PtdIns(4,5)P2 1. INPP5F functions as a negative regulator of insulin/AKT signaling, forming a protective feedback loop that is disrupted in diabetic cardiomyopathy by hyperglycemia and hyperlipidemia-induced NF-κB activation 2. In hepatocellular carcinoma, INPP5F undergoes cytoplasmic translocation and interacts with ASPH to activate Notch signaling, promoting tumor growth and metabolic reprogramming 3. The gene has significant disease relevance, with genetic variants associated with increased risk of both Parkinson's disease and Alzheimer's disease through altered brain expression 45. Additionally, INPP5F methylation alterations contribute to congenital heart disease with extracardiac malformations 6. These findings establish INPP5F as a critical regulator of membrane trafficking with broad implications for neurodegeneration, cardiovascular disease, and cancer through its effects on cellular signaling pathways.