AGPAT4 (1-acylglycerol-3-phosphate O-acyltransferase 4) is a mitochondrial outer membrane enzyme that catalyzes the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA) by incorporating acyl-CoA moieties, with particular specificity for polyunsaturated fatty acids like docosahexaenoic acid 1. The enzyme localizes to mitochondrial outer membranes and trans-Golgi network membranes, where it plays critical roles in membrane remodeling and phospholipid biosynthesis 12. In normal physiology, AGPAT4 regulates brain phospholipid composition, including phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol levels 2. However, AGPAT4 is aberrantly upregulated in multiple cancers and acts as an oncofetal protein promoting tumor progression. In colorectal cancer, elevated AGPAT4 supports tumor growth by suppressing LPA-mediated macrophage M1 polarization and T-cell activation 3. In hepatocellular carcinoma, AGPAT4 promotes tumor lineage plasticity and sorafenib resistance through mTOR/S6K signaling, and AGPAT4 inhibition synergizes with targeted therapy 4. AGPAT4 is also upregulated in endometriosis and thyroid carcinoma, correlating with poor prognosis 56. These findings establish AGPAT4 as a therapeutic target across multiple malignancies and non-neoplastic proliferative diseases.