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Crotonyllysine is a post-translational modification of protein lysine residues, characterized by the addition of a crotonyl group. This modification plays a crucial role in various cellular processes, including gene transcription, acute kidney injury, and spermatogenesis. The dynamic balance of crotonyllysine modification is regulated by a set of enzymes, including "writers" that add the modification and "erasers" that remove it. Crotonyl-CoA, the primary precursor for crotonyllysine modification, is influenced by the activity of enzymes such as ACSS2 and CDYL. Abnormal levels of crotonyl-CoA and crotonyllysine have been implicated in several diseases, including cancer and cardiovascular diseases, making it an important area of research for future therapeutic strategies.