Janus kinases (JAKs) are cytoplasmic tyrosine kinases. They link cytokine signalling from membrane receptors to signal transducers and activators of transcription (STAT) transcription factors. Four JAK family members are known: JAK1, JAK2, JAK3 and TYK2. The JAK–STAT signalling paradigm was discovered two decades ago, providing a breakthrough in the understanding of cytokine biology . JAKs associate with a proline-rich region in each intracellular domain, which is adjacent to the cell membrane and called a box1/box2 region. After the receptor associates with its respective cytokine/ligand, it goes through a conformational change, bringing the two JAKs close enough to phosphorylate each other.