Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that catalyzes the synthesis of very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty acids that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May play a critical role in early brain and skin development. a very-long-chain acyl-CoA + H(+) + malonyl-CoA = a very-long-chain 3-oxoacyl-CoA + CO2 + CoA H(+) + hexacosanoyl-CoA + malonyl-CoA = 3-oxooctacosanyol-CoA + CO2 + CoA H(+) + malonyl-CoA + octacosanoyl-CoA = 3-oxo-triacontanoyl-CoA + CO2 + CoA H(+) + malonyl-CoA + triacontanoyl-CoA = 3-oxo-dotriacontanoyl-CoA + CO2 + CoA (19Z,22Z,25Z,28Z,31Z)-tetratriacontapentaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(21Z,24Z,27Z,30Z,33Z)-hexatriacontapentaenoyl-CoA + CO2 + CoA (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + CO2 + CoA (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + H(+) + malonyl-CoA = (9Z,12Z,15Z,18Z)-3-oxotetracosatetraenoyl-CoA + CO2 + CoA (11Z,14Z,17Z,20Z,23Z)-hexacosapentaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(13Z,16Z,19Z,22Z,25Z)-octacosapentaenoyl-CoA + CO2 + CoA (13Z,16Z,19Z,22Z,25Z)-octacosapentaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(15Z,18Z,21Z,24Z,27Z)-triacontapentaenoyl-CoA + CO2 + CoA (15Z,18Z,21Z,24Z,27Z)-triacontapentaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(17Z,20Z,23Z,26Z,29Z)-dotriacontapentaenoyl-CoA + CO2 + CoA (17Z,20Z,23Z,26Z,29Z)-dotriacontapentaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(19Z,22Z,25Z,28Z,31Z)-tetratriacontapentaenoyl-CoA + CO2 + CoA (21Z,24Z,27Z,30Z,33Z)-hexatriacontapentaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(23Z,26Z,29Z,32Z,35Z)-octatriacontapentaenoyl-CoA + CO2 + CoA (11Z,14Z,17Z,20Z)-hexacosatetraenoyl-CoA + H(+) + malonyl-CoA = (13Z,16Z,19Z,22Z)-3-oxooctacosatetraenoyl-CoA + CO2 + CoA (13Z,16Z,19Z,22Z)-octacosatetraenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(15Z,18Z,21Z,24Z)-triacontatetraenoyl-CoA + CO2 + CoA (15Z,18Z,21Z,24Z)-triacontatetraenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(17Z,20Z,23Z,26Z)-dotriacontatetraenoyl-CoA + CO2 + CoA (17Z,20Z,23Z,26Z)-dotriacontatetraenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(19Z,22Z,25Z,28Z)-tetratriacontatetraenoyl-CoA + CO2 + CoA (19Z,22Z,25Z,28Z)-tetratriacontatetraenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(21Z,24Z,27Z,30Z)-hexatriacontatetraenoyl-CoA + CO2 + CoA (21Z,24Z,27Z,30Z)-hexatriacontatetraenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(23Z,26Z,29Z,32Z)-octatriacontatetraenoyl-CoA + CO2 + CoA (6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(8Z,11Z,14Z,17Z,20Z,23Z)-hexacosahexaenoyl-CoA + CO2 + CoA (8Z,11Z,14Z,17Z,20Z,23Z)-hexacosahexaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(10Z,13Z,16Z,19Z,22Z,25Z)-octacosahexaenoyl-CoA + CO2 + CoA (10Z,13Z,16Z,19Z,22Z,25Z)-octacosahexaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(12Z,15Z,18Z,21Z,24Z,27Z)-triacontahexaenoyl-CoA + CO2 + CoA (12Z,15Z,18Z,21Z,24Z,27Z)-triacontahexaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(14Z,17Z,20Z,23Z,26Z,29Z)-dotriacontahexaenoyl-CoA + CO2 + CoA (14Z,17Z,20Z,23Z,26Z,29Z)-dotriacontahexaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(16Z,19Z,22Z,25Z,28Z,31Z)-tetratriacontahexaenoyl-CoA + CO2 + CoA (16Z,19Z,22Z,25Z,28Z,31Z)-tetratriacontahexaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(18Z,21Z,24Z,27Z,30Z,33Z)-hexatriacontahexaenoyl-CoA + CO2 + CoA (9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoA + H(+) + malonyl-CoA = 3-oxo-(11Z,14Z,17Z,20Z,23Z)-hexacosapentaenoyl-CoA + CO2 + CoA Lipid metabolism; fatty acid biosynthesis. Oligomer. The C-terminal di-lysine motif confers endoplasmic reticulum localization. N-glycosylated. Belongs to the ELO family. ELOVL4 subfamily.