Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward very-long-chain fatty acyl-CoA (chain length C22-C27) (PubMed:15823095, PubMed:18165233, PubMed:20110363, PubMed:23275342). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:15823095, PubMed:18165233, PubMed:20110363, PubMed:23275342). Plays a non-redundant role in the synthesis of ceramides with very-long-chain fatty acids in kidney, liver and brain. Regulates the abundance of myelin-specific sphingolipids galactosylceramide and sulfatide that affects myelin sheath architecture and motor neuron functions (PubMed:19801672, PubMed:32279995). a sphingoid base + a very long-chain fatty acyl-CoA = an N-(very-long-chain fatty acyl)-sphingoid base + CoA + H(+) docosanoyl-CoA + sphinganine = CoA + H(+) + N-docosanoylsphinganine sphinganine + tetracosanoyl-CoA = CoA + H(+) + N-tetracosanoylsphinganine hexacosanoyl-CoA + sphinganine = CoA + H(+) + N-hexacosanoylsphinganine (15Z)-tetracosenoyl-CoA + sphinganine = CoA + H(+) + N-(15Z-tetracosenoyl)-sphinganine 2-hydroxytetracosanoyl-CoA + sphinganine = CoA + H(+) + N-(2-hydroxytetracosanoyl)-sphinganine 2-hydroxydocosanoyl-CoA + sphinganine = CoA + H(+) + N-(2-hydroxydocosanoyl)-sphinganine 2-hydroxytetracosenoyl-CoA + sphinganine = CoA + H(+) + N-(2-hydroxytetracosenoyl)-sphinganine sphinganine + tetracosenoyl-CoA = an N-tetracosenoylsphinganine + CoA + H(+) hexacosenoyl-CoA + sphinganine = CoA + H(+) + N-hexacosenoylsphinganine sphing-4-enine + tetracosanoyl-CoA = CoA + H(+) + N-tetracosanoyl-sphing-4-enine sphing-4-enine + tetracosenoyl-CoA = CoA + H(+) + N-(tetracosenoyl)-sphing-4-enine heptadecasphing-4-enine + tetracosanoyl-CoA = CoA + H(+) + N-tetracosanoyl-heptadecasphing-4-enine a fatty acyl-CoA + sphing-4-enine = an N-acylsphing-4-enine + CoA + H(+) hexadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N-hexadecanoylsphing-4-enine octadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N-octadecanoylsphing-4-enine eicosanoyl-CoA + sphing-4-enine = CoA + H(+) + N-eicosanoyl-sphing-4-enine hexadecanoyl-CoA + sphinganine = CoA + H(+) + N-hexadecanoylsphinganine octadecanoyl-CoA + sphinganine = CoA + H(+) + N-(octadecanoyl)-sphinganine (9Z)-octadecenoyl-CoA + sphinganine = CoA + H(+) + N-(9Z-octadecenoyl)-sphinganine eicosanoyl-CoA + sphinganine = CoA + H(+) + N-eicosanoylsphinganine Ceramide synthase activity is inhibited by sphingosine-1-phosphate. Lipid metabolism; sphingolipid metabolism. Interacts with ATP6V0C, ASGR1, ASGR2 and SLC22A1/OCT1. Interacts with ELOV1, HSD17B12 and TECR (By similarity). Interacts with NDUFS2 (PubMed:32279995). Broadly expressed, with highest levels in liver and kidney (PubMed:15823095, PubMed:18165233, PubMed:19801672). In brain is detected in neurons, oligodentrocytes, ependymal cells and epithelial cells of the choroid plexus. In kidney is detected in collecting ducts and to a lesser degree in proximal tubules. The last loop motif confers selectivity toward behenoyl-CoA (docosanoyl-CoA; C22:0-CoA) and lignoceroyl-CoA (tetracosanoyl-CoA; C24:0-CoA) as acyl donors. Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation (PubMed:26620563). Phosphorylated at the C-terminus by CK2, leading to increase the ceramide synthase activity. Most mice do not survive beyond 16 months (PubMed:20110363). Ceramide and downstream sphingolipids are devoid of very long (C22-C24) acyl chains (PubMed:20110363). Total glycerophospholipid and cholesterol levels are unaltered, while a marked increase in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids are observed (PubMed:20110363). Membranes display higher membrane fluidity and show morphological changes (PubMed:20110363). Mutant mice show signs of neurodegeneration characterized by the loss of myelin sheath structure stability and formation of numerous small cysts in the cerebellum. They develop hepatocarcinomas between 7 and 9 months of age. Contains a predicted homeobox domain which is degenerated and lacks residues that are important for DNA-binding. The protein localizes in the endoplasmic reticulum and not in the nucleus, which also argues against homeobox function (PubMed:15823095).