Human leukotriene C4 synthase (LTC4S), an 18kDa integral membrane protein and member of the MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family, is critical to the biosynthesis of the cysteinyl leukotrienes. LTC4S catalyzes the conjugation of leukotriene A4 with glutathione to produce leukotriene C4. The cysteinyl leukotrienes, in particular leukotriene C4 and its metabolites, are important lipid mediators in inflammation and are central to acute and chronic inflammatory diseases of the respiratory system, in particular bronchial asthma. The structure of human LTC4S was studied by two-dimensional (2D) crystallization and electron crystallography.When reconstituted into proteoliposomes under rigorously controlled parameters, human LTC4S forms large and well-ordered two-dimensional crystals that retain enzymatic activity. Despite two three-dimensional structure, many questions about the reaction mechanism of human LTC4S remain unanswered. To elucidate these structure/function questions by electron crystallography, we are crystallizing both the wild-type and mutant enzymes. Surprisingly, the number of subunits of human LTC4S is not limited to the trimers earlier observed by both electron and x-ray crystallography.