FADS3 (fatty acid desaturase 3) is a sphingoid base desaturase that introduces a cis double bond between carbon 14 and carbon 15 of sphingoid bases, producing sphinga-4,14-dienine (SPD, d18:2) from sphingosine 1. The enzyme preferentially acts on sphingosine-containing ceramides as substrates, though it can also metabolize free sphingosine 1. FADS3 activity contributes to gender differences in plasma sphingolipidome, with sphingadienine levels approximately 30% higher in females 1. The enzyme operates through an electron transfer mechanism facilitated by cytochrome b5 2. FADS3 may play a protective role in cellular detoxification by converting cytotoxic 1-deoxysphinganine to 1-deoxysphingosine, with overexpressing cells showing increased resistance to m18:0 toxicity 1. Located within the FADS gene cluster on chromosome 11-13.1, FADS3 is associated with cancer susceptibility, particularly in head and neck squamous cell carcinoma where upregulation correlates with poor prognosis and reduced CD8+ T cell infiltration 3. The gene shows tissue-specific expression patterns, with weak hepatic expression compared to lung and spleen 4, and genetic variants influence plasma sphingolipid ratios 1.