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 exhibits activity toward saturated and unsaturated acyl-CoA substrates with higher activity toward C18 acyl-CoAs, especially C18:0 acyl-CoAs. May participate in the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Participates in the formation of certain VLCFA and triglycerides in certain cells of the hair follicles and the sebaceous glands, required for skin barrier function. Critical enzyme for lipid accumulation and metabolic activity in brown adipocytes during the early phase of the tissue recruitment. Plays a role in lipid storage and in resistance to diet-induced obesity. a very-long-chain acyl-CoA + H(+) + malonyl-CoA = a very-long-chain 3-oxoacyl-CoA + CO2 + CoA eicosanoyl-CoA + H(+) + malonyl-CoA = 3-oxodocosanoyl-CoA + CO2 + CoA H(+) + hexadecanoyl-CoA + malonyl-CoA = 3-oxooctadecanoyl-CoA + CO2 + CoA H(+) + malonyl-CoA + octadecanoyl-CoA = 3-oxoeicosanoyl-CoA + CO2 + CoA (9Z)-octadecenoyl-CoA + H(+) + malonyl-CoA = (11Z)-3-oxoicosenoyl-CoA + CO2 + CoA (9Z,12Z)-octadecadienoyl-CoA + H(+) + malonyl-CoA = (11Z,14Z)-3-oxoicosa-11,14-dienoyl-CoA + CO2 + CoA (9Z,12Z,15Z)-octadecatrienoyl-CoA + H(+) + malonyl-CoA = (11Z,14Z,17Z)-3-oxoeicosatrienoyl-CoA + CO2 + CoA docosanoyl-CoA + H(+) + malonyl-CoA = 3-oxotetracosanoyl-CoA + CO2 + CoA H(+) + malonyl-CoA + tetradecanoyl-CoA = 3-oxohexadecanoyl-CoA + CO2 + CoA Lipid metabolism; polyunsaturated fatty acid biosynthesis. Expressed in brown adipose tissue and liver. In the skin, strong expressed in the cells of the inner layer of the outer root sheath of the hair follicles and in the sebocytes of the sebaceous glands. Hardly detectable in the epidermis and not at all in fibroblasts. Strongly up-regulated in brown adipose tissue in conditions of brown fat recruitment, such as cold stress, perinatal development and after diet-induced thermogenesis. A synergistic action of both catecholamines and glucocorticoids is required for the induction. N-Glycosylated. Mutant mice grow normally and are fertile. They display a sparse hair coat, a hyperplastic pilosebaceous system and their hair lipid content is disturbed with exceptionally high levels of eicosenoic acid (20:1). In the triglyceride fraction, fatty acids longer than 20 carbon atoms are almost undetectable. As a result, mice exhibited a severe defect in water repulsion and increased trans-epidermal water loss. When exposed to cold stress, mutants exhibit a significantly reduced VLCFA elongation activity in brown adipose tissue, but only during the initial phase. Cold-acclimated mutants are equally efficient as normal mice at elongating fatty acids. Mutant mice are lean and resistant to diet-induced weight gain, they show normal food intake but increased metabolic rate, and show reduced hepatic lipogenesis and triglycerides synthesis. Belongs to the ELO family. ELOVL3 subfamily.