Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA) (PubMed:17977534, PubMed:23530041, PubMed:26887952, PubMed:31916624). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:17977534, PubMed:23530041, PubMed:26887952, PubMed:31916624, PubMed:24782409). Plays a predominant role in skeletal muscle in regulating C18 ceramide and dihydroceramide levels with an impact on whole-body glucose metabolism and insulin sensitivity. Protects from diet-induced obesity by suppressing the uptake of glucose in multiple organs in a FGF21-dependent way (By similarity). Generates C18 ceramides in the brain, playing a critical role in cerebellar development and Purkinje cell function (By similarity). In response to cellular stress mediates mitophagy, a known defense mechanism against cell transformation and aging. Upon mitochondria fission, generates C18 ceramides that anchor lipidated MAP1LC3B/LC3B-II autophagolysosomes to outer mitochondrial membranes to eliminate damaged mitochondria (PubMed:22922758). a sphingoid base + octadecanoyl-CoA = an N-octadecanoyl-sphingoid base + CoA + H(+) octadecanoyl-CoA + sphinganine = CoA + H(+) + N-(octadecanoyl)-sphinganine hexadecasphinganine + octadecanoyl-CoA = CoA + H(+) + N-octadecanoylhexadecasphinganine octadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N-octadecanoylsphing-4-enine heptadecasphing-4-enine + octadecanoyl-CoA = CoA + H(+) + N-octadecanoyl-heptadecasphing-4-enine 2-hydroxyoctadecanoyl-CoA + sphinganine = CoA + H(+) + N-(2-hydroxyoctadecanoyl)-sphinganine eicosanoyl-CoA + sphinganine = CoA + H(+) + N-eicosanoylsphinganine Inhibited by fumonisin B1. Lipid metabolism; sphingolipid metabolism. Acetylated. Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation. The disease is caused by variants affecting the gene represented in this entry. This protein is produced by a bicistronic gene which also produces the GDF1 protein from a non-overlapping reading frame.