Acts as a front-end fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 5 located between a preexisting double bond and the carboxyl end of the fatty acyl chain. Involved in biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors. Specifically, desaturates dihomo-gamma-linoleoate (DGLA) (20:3n-6) and eicosatetraenoate (ETA) (20:4n-3) to generate arachidonate (AA) (20:4n-6) and eicosapentaenoate (EPA) (20:5n-3), respectively (Probable). As a rate limiting enzyme for DGLA (20:3n-6) and AA (20:4n-6)-derived eicosanoid biosynthesis, controls the metabolism of inflammatory lipids like prostaglandin E2, critical for efficient acute inflammatory response and maintenance of epithelium homeostasis. Contributes to membrane phospholipid biosynthesis by providing AA (20:4n-6) as a major acyl chain esterified into phospholipids. In particular, regulates phosphatidylinositol-4,5-bisphosphate levels, modulating inflammatory cytokine production in T-cells (By similarity). Also desaturates (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a metabolite in the biohydrogenation pathway of LA (18:2n-6) (By similarity). Does not exhibit any catalytic activity toward 20:3n-6, but it may enhance FADS2 activity. (8Z,11Z,14Z)-eicosatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (8Z,11Z,14Z,17Z)-eicosatetraenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (5Z,11E)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O Lipid metabolism; polyunsaturated fatty acid biosynthesis. Widely expressed. Expressed in brain, liver and thymus (at protein level). Isoform 1 seems to be more abundant than isoform 2. Expression of isoform 2 is very low in spleen and not detectable in skeletal muscle. The histidine box domains may contain the active site and/or be involved in metal ion binding. Belongs to the fatty acid desaturase type 1 family.