Tyk2 was the first member of the JAK family that was described (the other members are JAK1, JAK2, and JAK3). It has been implicated in IFN-α, IL-6, IL-10 and IL-12 signaling. Tyk2 functions primarily in IL-12 and type I-IFN signaling. Tyk2 deficiency has more dramatic effects in human cells than in mouse cells. However, in addition to IFN-α and -β and IL-12 signaling, Tyk2 has major effects on the transduction of IL-23, IL-10, and IL-6 signals. Recently, it has been recognized that IL-12 and IL-23 share ligand and receptor subunits that activate Tyk2. Tyk2 is activated by IL-10, and its deficiency affects the ability to generate and respond to IL-10.