CD89 (FCAR) is a variably glycosylated 50-100 kDa myeloid-specific type I transmembrane (TM) Fc receptor for IgA that is a member of the multichain immune recognition receptor (MIRR) family. Human CD89 contains a 21 amino acid (aa) signal sequence and extracellular (ECD), TM and cytoplasmic domains of 206, 19 and 41 aa, respectively. Arg230 within the TM domain supports interaction with the ITAM-containing signaling subunit, FcR gamma, which contains a TM Asp . Two ECD C2-type Ig-like domains (EC1 and 2) are oriented at right angles. Up to two molecules of FCAR can bind one molecule of serum IgA via EC1. Many splice variants have been reported, but only two have been identified as proteins. The a.2 form, which lacks 22 aa just prior to the TM domain, is exclusively expressed in alveolar macrophages. The a.3 form lacks EC2. FCAR binds monomeric, polymeric and secretory IgA, but does not mediate the barrier function of secretory IgA in mucosal epithelium. CD89 (Fc alphaRI) is the human myeloid IgA Fc receptor expressed on cells, such as neutrophils, eosinophils and monocytes/macrophages. Cross-linking of CD89 on these cells, by IgA-opsonised particles (e.g. bacteria, viruses) or anti-CD89 monoclonal antibodies, can trigger various immunological effector functions which are generally protective but may also cause harm to the body.