SPTLC3 (serine palmitoyltransferase long chain base subunit 3) is a specialized catalytic component of the serine palmitoyltransferase (SPT) enzyme complex that determines substrate specificity in sphingolipid biosynthesis 1. Unlike the ubiquitously expressed SPTLC1 and SPTLC2 subunits, SPTLC3 shows restricted tissue expression and generates structurally distinct sphingolipids with shorter chain lengths 2. The SPTLC1-SPTLC3 heterodimer produces C16-sphinganine and C16-sphingosine, creating approximately 15% of human plasma sphingolipids, while also utilizing C14-CoA substrates more efficiently than SPTLC2-containing complexes 1. SPTLC3 expression is induced under pathological conditions, particularly in ischemic cardiomyopathy where it is transcriptionally regulated by HIF1α and contributes to mitochondrial complex I dysfunction, oxidative stress, and cardiac dysfunction 3. The enzyme also plays roles in metabolic diseases, with genetic variants like rs364585 associated with altered serum lipid profiles 4. SPTLC3 is notably expressed in specific tissues like urinary bladder epithelium, where it contributes to phytoceramide production important for membrane properties 5. Its dysregulation has been implicated in cardiovascular disease progression through altered sphingolipid metabolism and lipoprotein trafficking 6.