PLPP4 is a magnesium-independent phospholipid phosphatase that preferentially converts diacylglycerol pyrophosphate to phosphatidate, with broader activity on phosphatidate and lysophosphatidate 1. As a lipid metabolic enzyme, it participates in both lipid synthesis and the generation of lipid-signaling molecules including diacylglycerol. In breast cancer cells, PLPP4 acts as an oncogene by enhancing lipid accumulation, triacylglycerol metabolism, and adipogenic potential through upregulation of markers such as PPARγ and perilipin 1 2. PLPP4 knockdown in breast cancer reduces proliferation, migration, and invasion while improving doxorubicin sensitivity; transcription factor CAPRIN1 regulates PLPP4 expression to modulate these cancer cell properties 3. In lung carcinoma, elevated PLPP4 correlates with poor survival outcomes, and its silencing inhibits proliferation and tumorigenesis by reducing calcium influx 4. PLPP4 is also identified as a ferroptosis-related biomarker in temporal lobe epilepsy and as a potential driver of epithelial-mesenchymal transition 56. Population-level association studies nominate PLPP4 variants in Parkinson's disease and identify it among genes overexpressed in ovarian cancer bowel metastases 78. These findings suggest PLPP4 inhibition as a potential therapeutic strategy to enhance chemotherapy efficacy in cancer patients.