Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:17681178, PubMed:24269233, PubMed:22633490). ACSL5 may activate fatty acids from exogenous sources for the synthesis of triacylglycerol destined for intracellular storage (By similarity). Utilizes a wide range of saturated fatty acids with a preference for C16-C18 unsaturated fatty acids (By similarity). It was suggested that it may also stimulate fatty acid oxidation (By similarity). At the villus tip of the crypt-villus axis of the small intestine may sensitize epithelial cells to apoptosis specifically triggered by the death ligand TRAIL. May have a role in the survival of glioma cells. a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate ATP + CoA + hexadecanoate = AMP + diphosphate + hexadecanoyl-CoA (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate Optimum pH is 9.5. Optimum pH is 7.5-8.5. Localize in mitochondrion and endoplasmic reticulum. Localize in mitochondrion and endoplasmic reticulum. Belongs to the ATP-dependent AMP-binding enzyme family.