Interleukin 4 Receptor alpha (IL4-Ra) is a widely expressed 140 kDa transmembrane glycoprotein in the class I cytokine receptor family. Mature human IL4-Ra consists of a 207 amino acid (aa) extracellular domain (ECD) that contains a cytokine binding region and one fibronectin type III domain, a 24 aa transmembrane segment, and a 569 aa cytoplasmic domain that contains one Box 1 motif and one ITIM motif. IL4-Ra plays an important role in Th2-biased immune responses, alternative macrophage activation, mucosal immunity, allergic inflammation, tumor progression, and atherogenesis. Soluble forms of IL4-Ra, generated by alternate splicing or proteolysis, retain ligand binding properties and inhibit IL-4 bioactivity. IL4-Ra is a component of two distinct receptor complexes and shows species selectivity between human and mouse. It can associate with the common gamma chain (γc) to form the IL-4 responsive type I receptor in which γc increases the affinity for IL-4 and enables signaling. It can alternatively associate with IL13-Ra1 to form the type II receptor which is responsive to both IL-4 and IL-13. The use of shared receptor components contributes to the overlapping biological effects of IL-4 and IL-13 as well as other cytokines that utilize γc.