Post-translational modifications (PTMs) represent a crucial means of regulating diverse biological processes and cellular physiology by influencing protein structure and function. Histone lysine lactylation (Kla) is a newly discovered histone modification, which regulates gene expression in macrophages. In M1 macrophages, lactate is derived from incompletely oxidized glucose and then generate lactyl-CoA, which is transferred to lysine tails of histone proteins via the acetyl transferase p300. This modification was high in gene promoter regions that lack acetylation and associated with activation of genes expression. As a large number of studies have demonstrated that lysine acylation possessed a diverse range of substrate proteins, however, no systematic analysis has been reported for lysine lactylation.