DGKH encodes diacylglycerol kinase eta, an enzyme that converts diacylglycerol (DAG) into phosphatidic acid (PA), thereby switching between signaling pathways activated by these second messengers. DGKH promotes cell growth by activating the Ras/B-Raf/C-Raf/MEK/ERK signaling pathway induced by EGF and regulates RAF1 and BRAF recruitment and heterodimerization at membranes. Recent evidence reveals DGKH's role in cancer progression. In hepatocellular carcinoma (HCC), DGKH expression is elevated in tumor tissue compared to normal tissue, and higher DGKH expression correlates with undifferentiated tumors and reduced responsiveness to tyrosine kinase inhibitors 1. Mechanistically, DGKH promotes mTOR signaling through phosphatidic acid production, and combined sorafenib and DGKH depletion significantly reduced tumor burden and cancer stemness in mouse models 1. Additionally, DGKH activation occurs in Philadelphia chr13-like acute lymphoblastic leukemia, a high-risk ALL subset 2. Genetic variants in DGKH associate with neuropsychiatric and metabolic disorders. A risk haplotype spanning exons 65–243 is associated with bipolar disorder, unipolar depression, and adult ADHD, suggesting a shared biological mechanism related to mood instability 3. DGKH polymorphisms also link to calcium oxalate kidney stone formation and hypercalciuria 4. In diabetic peripheral neuropathy, elevated Dgkh expression triggers Schwann cell apoptosis through PKC-α inhibition 5.