p97-mediated proteostasis is a checkpoint for late-stage thymocyte positive selection.

p97 is essential for late-stage thymocyte positive selection, with its loss causing a severe blockade in CD8+ lineage commitment and thymocyte development.

• Why it matters: Understanding the mechanisms behind thymocyte maturation is crucial for insights into immune system development and potential immunodeficiencies, yet p97's role in this process was previously unclear.
• What they did: Researchers used genetic deletion and pharmacological inhibition of p97 in mice to investigate its function, revealing stage- and lineage-specific effects, especially in double-positive thymocytes.
• The result: Loss of p97 causes proteostatic collapse, impairs IL-7R signaling, and leads to thymocyte apoptosis, but JAK activation can partially rescue thymocyte development, highlighting p97's critical role in immune cell maturation.