Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward very- and ultra-long-chain fatty acyl-CoA (chain length greater than C22) (PubMed:17977534, PubMed:22038835, PubMed:26887952). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:17977534, PubMed:22038835, PubMed:26887952). It is crucial for the synthesis of ultra-long-chain ceramides in the epidermis, to maintain epidermal lipid homeostasis and terminal differentiation (PubMed:23754960). 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 2-hydroxydocosanoyl-CoA + sphinganine = CoA + H(+) + N-(2-hydroxydocosanoyl)-sphinganine 2-hydroxytetracosanoyl-CoA + sphinganine = CoA + H(+) + N-(2-hydroxytetracosanoyl)-sphinganine a sphingoid base + an ultra-long-chain fatty acyl-CoA = an N-(ultra-long-chain-acyl)-sphingoid base + CoA + H(+) octacosanoyl-CoA + sphinganine = CoA + H(+) + N-(octacosanoyl)-sphinganine a fatty acyl-CoA + sphing-4-enine = an N-acylsphing-4-enine + CoA + H(+) octadecanoyl-CoA + sphinganine = CoA + H(+) + N-(octadecanoyl)-sphinganine 2-hydroxyoctadecanoyl-CoA + sphinganine = CoA + H(+) + N-(2-hydroxyoctadecanoyl)-sphinganine Lipid metabolism; sphingolipid metabolism. Expressed in the epidermis, where it localizes at the interface between the stratum granulosum and the stratum corneum (at protein level). The disease is caused by variants affecting the gene represented in this entry. Contains a predicted homeobox domain which is degenerated, lacking residues important for DNA-binding. Moreover, the protein localizes in the endoplasmic reticulum and not in the nucleus, which also argues against homeobox function (By similarity).