{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ceramide kinase (CERK) is a lipid‐modifying enzyme that phosphorylates ceramide to generate ceramide‑1‑phosphate (C1P), a bioactive sphingolipid serving as a critical signaling mediator in diverse cellular processes. Early molecular cloning and biochemical analyses revealed that CERK possesses a diacylglycerol kinase–like catalytic domain together with a pleckstrin homology domain that is essential for its proper membrane targeting, substrate specificity, and overall enzymatic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Through the generation of C1P, CERK regulates the activation of group IVA cytosolic phospholipase A₂, thereby promoting arachidonic acid release and downstream eicosanoid synthesis in response to inflammatory agonists such as cytokines and calcium ionophores."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In immune cells, CERK‐derived C1P modulates plasma membrane biophysical properties—contributing to the formation of ordered lipid raft domains that facilitate membrane fusion during phagocytosis—and also exerts anti‐inflammatory effects by directly inhibiting TNF‑α–converting enzyme (TACE), which attenuates cytokine secretion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Studies employing CERK‑null models further emphasize its role in maintaining lipid homeostasis, regulating neutrophil survival and function, and modulating metabolic as well as immune responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " Collectively, these findings establish CERK as a pivotal enzyme linking ceramide metabolism to key signal transduction pathways that govern inflammation, cell survival, and membrane dynamics—with important implications for pathological states ranging from metabolic disorders and cancer to neuroinflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masako Sugiura, Keita Kono, Hong Liu, et al. 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