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). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:12105227, PubMed:16951403, PubMed:17977534, PubMed:18541923, PubMed:30605666). 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 (PubMed:30605666). Generates C18 ceramides in the brain, playing a critical role in cerebellar development and Purkinje cell function (PubMed:21625621). 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 (By similarity). 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. Expressed in brain, skeletal muscle, heart and perigonadal white adipose tissue. Up-regulated in skeletal muscle in response to high-fat diet. Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation (PubMed:26620563). Defects in CERS1 cause cerebellar ataxia and Purkinje cell degeneration. Two mouse strains flincher (fln) and toppler (to) carry spontaneous recessive mutations at the TLC domain of CERS1, resulting in complete loss of the catalytic activity associated with a reduction in sphingolipid biosynthesis and accumulation of lipofuscin in many brain regions. This protein is produced by a bicistronic gene which also produces the GDF1 protein from a non-overlapping reading frame.