Clinical targeting of mast cell functions. There are various extracellular cytokines that are released from mast cells or that regulate the mast cell responses after binding to their corresponding receptors on mast cells. Some of these cytokines have been targeted using blocking monoclonal antibodies, which are in use to treat allergic disorders such as asthma. These cytokines include TNF, IL-1, IL-5, IL-9, IL-13, IL-17A, IL-33, GM-CSF, and thymic stromal lymphopoietin (TSLP). Furthermore, extracellular IgE is targeted with Omalizumab, and histamine is targeted with antihistamines. Similarly, many cell-surface receptors involved in mast cell activation are also therapeutic targets. These receptors include IL-4Rα (a common receptor for IL-4 and IL-13), cysteinyl leukotriene receptor 1 (CYSLTR1), and β-2 adrenergic receptor (ADRB2). Intracellular targets in mast cells include Syk kinase (mediating LAT phosphorylation and signal propagation), intracellular calcium, arachidonate 5–lipoxygenase (ALOX5; important for leukotriene synthesis), cyclooxygenase 2 (COX-2; important for prostaglandin synthesis), calcineurin (phosphatase activating NFAT TF), and the glucocorticoid receptor (inhibiting proinflammatory cytokine synthesis). Inhibitory receptor Siglec 8 is also another therapeutic target. Promising future therapies might also include the use of antisense oligonucleotides, DNAzymes, and small-molecule inhibitors of MRGPRX2 receptor activation.