TNK1 is a targetable JAK-independent driver of STAT signaling and inflammation.

TNK1 is a JAK-independent kinase that directly activates STAT1, driving inflammation and colitis in mice, revealing a new therapeutic target.

• Why it matters: Understanding alternative pathways of STAT activation is crucial because JAK-dependent mechanisms do not fully explain inflammatory diseases like colitis, limiting treatment options.
• What they did: Using multiomics, the study identified TNK1 as a kinase that phosphorylates STAT1 independently of JAKs, interacts with STAT1 in cytosolic condensates, and requires a proline-rich region for activation.
• The result: Inhibiting TNK1 reduces STAT1 activity and alleviates colitis symptoms in mice, suggesting targeting TNK1 could offer new treatments for inflammatory diseases.