The alpha subunit of the high affinity IgE receptor (Fc epsilon  RI alpha or Fc epsilon RIA) is an IgE‑binding type I transmembrane glycoprotein of the multichain immune recognition (MIRR) family (1, 2). The receptor, Fc epsilon  RI, is a tetrameric complex of one alpha, one beta and two gamma subunits ( alpha beta gamma ₂) on mast cells and basophils (1). An alternate trimeric form ( alpha gamma ₂) is expressed on human, but not rodent, mast cells, basophils, eosinophils and professional antigen presenting cells (3). While the gamma subunit is essential for expression of Fc epsilon  RI alpha on the cell surface and for cell signaling, the beta subunit, when present, increases the halflife of the Fc epsilon  RI complex on the cell surface (3, 4). An isoform of the beta subunit, beta T, blocks processing of the alpha subunit and its cell surface expression (2, 3, 5). Human Fc epsilon  RI alpha cDNA encodes 257 amino acids (aa) including a 25 aa signal sequence, a 180 aa extracellular domain containing two Ig‑like domains that bind IgE and an endoplasmic reticulum retention motif, a 21 aa transmembrane domain with a charged amino acid (Asp219) that contributes to intracellular transport, and a 32 aa cytoplasmic sequence (1, 3, 6). Human Fc epsilon  RI alpha shares 50‑62% aa sequence identity with mouse, rat, equine, ovine, bovine, porcine and canine Fc epsilon  RI alpha. Binding of IgE alone increases surface expression of Fc epsilon  RI, while crosslinking of IgE/Fc epsilon  RI complexes by IgE ligands (allergens) initiates receptor internalization and signaling (2, 4, 5). Mast cell and basophil activation by IgE/Fc epsilon  RI crosslinking causes degranulation, releasing histamine, leukotrienes, prostaglandins, and other mediators of immediate‑type and late‑phase allergic reactions. Circulating autoantibodies that crosslink Fc epsilon  RI alpha are often found in patients with chronic urticaria (7). Fc epsilon  RI on human antigen presenting cells mediates uptake and processing of allergens for presentation by class II MHC (2, 3). Fc epsilon  RI expression on human DC and Langerhans cells is up‑regulated during allergic reactions (atopy) and correlates with serum IgE concentration (3).