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Histone lysine 2-hydroxyisobutyrylation (Khib) was identified as a novel posttranslational modification in 2014. Significant progress has been made in understanding its roles in reproduction, development, and disease. Although 2-hydroxyisobutyrylation shares some overlapping modification sites and regulatory factors with other lysine residue modifications, its unique structure suggests distinct functions. This review summarizes the latest advancements in Khib, including its regulatory mechanisms, roles in mammalian physiological processes, and its relationship with diseases. This provides direction for further research on Khib and offers new perspectives for developing treatment strategies for related diseases.
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