Human Jagged 2 is a 131 kDa (predicted) member of the Delta-Serrate-Lag-2 (DSL) family of ligands. This family activates LIN12/Notch proteins and thereby regulates cell fate determination during development (1 - 5). It is a type 1 transmembrane protein that is synthesized as a 1238 amino acid (aa) precursor (SwissProt # Q9Y219). It contains a 23 aa signal sequence, a large 1057 aa extracellular region, a 21 aa transmembrane region, and a short 137 aa cytoplasmic region. The extracellular region contains four potential N-linked glycosylation sites, a DSL domain, 16 EGF-like repeats (many of which are also sites of calcium binding), a von Willebrand factor (vWF) type C domain, and a cysteine-rich region just proximal to the transmembrane segment (2). There are two isoforms for human Jagged 2, named long and short. The short form lacks a splicing variant region (aa 421 - 461) that is present in the long form of the protein. Human Jagged 2 shares 90% and 87% aa sequence identity with mouse and rat Jagged 2, respectively. During murine embryonic development, Jagged 2 is expressed highest in fetal thymus, epidermis, foregut, dorsal root ganglia, and inner ear (2). In 2-week old mice, the Jagged 2 transcript is most abundant in heart, lung, thymus, skeletal muscle, brain, and testis (2). Functionally, it is suggested that Jagged 2 engages the Notch1 pathway of signal transduction (2). It is involved in the development of the mammalian limb, branchial arches, central and peripheral nervous systems, T cell lineage differentiation, natural killer cells, and the establishment of functional natural killer cell lines (3, 5, 6).