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KLHL6: a proteostatic guardian against T-cell exhaustion

Yang Pu¹, Xuetao Cao²

¹Department of Physiology, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.

Trends in Immunology

|March 18, 2026

Abstract

None:

Cheng et al.'s recent study identifies the Cullin3-RING E3 ubiquitin ligase complexes (CRL3) adaptor protein Kelch-like protein 6 (KLHL6) as a proteostasis regulator whose downregulation in chronically stimulated T cells leads to the accumulation of thymocyte selection-associated high mobility group box protein and phosphoglycerate mutase family member 5, driving T-cell dysfunction. This work positions T-cell exhaustion as a proteostatic disorder and highlights KLHL6 as a promising target for cancer immunotherapy.

Keywords:

KLHL6 T-cell exhaustion ubiquitination

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