DGKZ (diacylglycerol kinase zeta) is a lipid kinase that catalyzes ATP-dependent conversion of diacylglycerol to phosphatidic acid, regulating cellular signaling through lipid metabolism 1. The enzyme localizes to multiple cellular compartments including the plasma membrane, cytosol, nucleus, and lamellipodium, where it negatively regulates T cell receptor signaling and intracellular signal transduction 1. Mechanistically, DGKZ promotes TGFβ signaling by suppressing caveolin/lipid raft-dependent endocytosis of TGFβR2, thereby stabilizing the receptor and activating the TGFβ/Smad3 pathway 2. The phosphatidic acid product modulates plasma membrane fluidity and receptor partitioning in lipid rafts 2. DGKZ also influences T cell activation by modulating diacylglycerol availability, with loss-of-function mutations reducing T cell cytokine production 3. Clinically, elevated DGKZ expression associates with poor prognosis in triple-negative breast cancer and acute myeloid leukemia, where knockdown induces apoptosis through MAPK/survivin/caspase pathway activation 42. Genetic variants in DGKZ are implicated in schizophrenia susceptibility through lipid signaling dysregulation 5, food protein-induced enterocolitis syndrome via epithelial barrier disruption 6, autism spectrum disorder 7, and HTLV-1-associated adult T-cell leukemia-lymphoma as a potential tumor suppressor 8. DGKζ inhibition represents a therapeutic strategy to enhance PD-1 checkpoint and CAR T-cell immunotherapies 1.