The 5-lipoxygenase-activating protein (FLAP), encoded by the *ALOX5AP* gene, is a critical mediator in the leukotriene biosynthesis pathway. Discovered in the 1990s, FLAP facilitates the interaction between 5-lipoxygenase (5-LO) and arachidonic acid, a key step in producing pro-inflammatory leukotrienes (LTs) like LTB4 and cysteinyl-LTs. These lipid mediators drive inflammatory responses in diseases such as asthma, atherosclerosis, and rheumatoid arthritis. FLAP’s role involves anchoring 5-LO to the nuclear membrane, enabling substrate transfer and enzyme activation. Genetic studies link *ALOX5AP* polymorphisms to increased cardiovascular and inflammatory disease risks, highlighting its therapeutic relevance. FLAP inhibitors, like MK-886. were developed to block LT synthesis, showing efficacy in preclinical models. However, clinical translation faced challenges due to off-target effects. FLAP-specific antibodies remain vital tools for studying protein localization, expression levels, and mechanistic interactions in cellular and tissue models. Recent research explores FLAP's involvement in viral infections (e.g., COVID-19) and cancer, broadening its pathophysiological significance. Despite setbacks in drug development, FLAP remains a promising target for modulating inflammation, with ongoing studies aiming to refine inhibitors and biologics for precision therapies.