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Ceramide transfer protein (CERT) is a 68-kDa cytosolic protein encoded by the CERT1 or COL4A3BP gene, containing an N-terminal pleckstrin homology (PH) domain (targeting to the Golgi via PI4P binding), a central FFAT motif (interacting with VAP proteins at the ER), and a C-terminal steroidogenic acute regulatory protein-related lipid transfer (START) domain (binding and shuttling ceramide molecules). CERT specifically transports ceramide from the ER to the trans-Golgi in a nonvesicular, ATP-dependent process, making it essential for normal sphingomyelin synthesis and overall sphingolipid balance in cells. Its function is tightly regulated by phosphorylation and protein-protein interactions, and its dysregulation is linked to diseases such as cancer and metabolic disorders due to impacts on apoptosis, cell growth, and signaling pathways.
Experimental CERT inhibitors block ceramide transport to the Golgi, leading to ceramide accumulation, which can induce apoptosis and alter cell proliferation (a potential anti-cancer strategy)
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