Daniella M. Schwartz

TL;DR: The Janus kinase (JAK)-signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules.

TL;DR: The biology of JAKs is discussed from a translational perspective, focusing on recent insights from clinical trials, the development of novel agents and the use of jakinibs in a spectrum of immune and inflammatory diseases.

TL;DR: The ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease.

TL;DR: A new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflammation is described, which resembles Behçet's disease.

TL;DR: The JAK–STAT pathway is described, its role in autoimmunity is outlined, and the rationale/pre-clinical evidence for targeting JAK-STAT signaling is explained, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation JakinIBs.