Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) (PubMed:15823095, PubMed:18541923, PubMed:23760501, PubMed:31150623). Can use other acyl donors, but with less efficiency (PubMed:18541923). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively. Ceramides generated by CERS6 play a role in inflammatory response (PubMed:22544924). Acts as a regulator of metabolism and hepatic lipid accumulation (PubMed:25295788, PubMed:30655217, PubMed:31150623). Under high fat diet, palmitoyl- (C16:0-) ceramides generated by CERS6 specifically bind the mitochondrial fission factor MFF, thereby promoting mitochondrial fragmentation and contributing to the development of obesity (PubMed:31150623). a sphingoid base + hexadecanoyl-CoA = an N-hexadecanoyl-sphingoid base + CoA + H(+) hexadecanoyl-CoA + sphinganine = CoA + H(+) + N-hexadecanoylsphinganine hexadecanoyl-CoA + hexadecasphinganine = CoA + H(+) + N-hexadecanoylhexadecasphinganine hexadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N-hexadecanoylsphing-4-enine sphinganine + tetradecanoyl-CoA = CoA + H(+) + N-(tetradecanoyl)-sphinganine octadecanoyl-CoA + sphinganine = CoA + H(+) + N-(octadecanoyl)-sphinganine Lipid metabolism; sphingolipid metabolism. Broadly expressed, with highest levels in kidney and brain (at protein level). Up-regulated in liver in response to high-fat diet. N-glycosylated (PubMed:15823095, PubMed:23760501). Glycosylation on Asn-18 is not necessary for function (PubMed:15823095). Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation (PubMed:26620563). Phosphorylated at the C-terminus by CK2. Mice show behavioral abnormalities including a clasping abnormality of their hind limbs and a habituation deficit (PubMed:23760501). Knockout mice are protected against high fat diet-induced obesity and glucose intolerance (PubMed:25295788, PubMed:31150623). Mice show decreased palmitoyl (C16:0) ceramide pools and increased energy expenditure (PubMed:25295788, PubMed:31150623). Conditional deletion in brown adipose tissue or liver also protects mice against high fat diet-induced obesity, while it is not the case with specific deletion in myeloid cells (PubMed:25295788). Some prediction bioinformatics tools predict the presence of a homeobox domain (By similarity). However, the domain is degenerate and residues that are important for DNA-binding are absent (By similarity). Moreover, the protein localizes in the endoplasmic reticulum and not in the nucleus, strongly suggesting that it does not constitute a canonical homeobox domain (PubMed:15823095).