The regulation of 5-lipoxygenase (5-LO) activity occurs at multiple steps and is quite complex; each of the regulatory steps has been the subject of intense investigation. Regulation of 5-LO product output is known to occur by regulation of availability and catalytic action of 5-LO. With respect to 5-LO protein availability there are data documenting regulation at the level of gene transcription (1–4), gene translation (5), and gene product translocation within the cell (6, 7). With respect to catalytic action, regulation of 5-LO product production is known to be influenced by the availability of its major substrate arachidonic acid (8). Another mechanism regulating 5-LO catalytic activity is termed suicide inactivation and results from the oxidative inactivation of the functional enzyme by its primary catalytic product, leukotrienne A4 (LTA4). Suicide inactivation is irreversible and occurs only when 5-LO is catalytically active (9). Thus, if a cell with catalytically active 5-LO is to sustain product output, there must be a means by which to replace the inactivated enzyme. Since 5-LO output is known to be sustained, de novo production of the enzyme must take place; therefore, it is critical to examine the factors regulating 5-LO gene transcription and translation. Indeed, among these points of regulation of 5-LO gene transcription and translation, we have identified a novel mechanism potentially accounting for variability of 5-LO transcriptional regulation among individuals, namely genetic variation due to mutations in the 5-LO core promoter. We review effects of these mutations in the context of regulation of 5-LO gene transcription.