Protein lactylation

Protein lactylation is a newly discovered post-translational modification whereby lactate is enzymatically or non-enzymatically attached to lysine residues on proteins, especially histones[1][2][3][5][6][7][8][9]. This process serves as an epigenetic signal that regulates gene transcription, chromatin structure, and protein function. Most forms of protein lactylation described to date involve lysine residues (lysine lactylation, Kla), with histone lactylation being the best characterized. Key enzymes identified as “writers” for lactylation include p300, CBP, KAT8, and YiaC in bacteria[2][8]. Lactylation impacts diverse biological processes such as tumor growth, immune response, inflammation, cell differentiation, neural activity, and tissue repair[1][3][5][7][9]. Aberrant lactylation contributes to diseases including cancer, inflammation, and neurodegeneration. Its regulatory mechanisms, biological functions, and therapeutic potential are active areas of research, but protein lactylation itself is neither a single protein target nor a traditional receptor—it is a modification occurring on many protein substrates in various contexts.

Other names

Lysine lactylationhistone lactylationKla

Enzyme inhibitors (e.g., p300/CBP inhibitors) reduce lactylation levels on histone and non-histone targets; Potential indirect effects via modulation of cellular lactate concentration or lactate metabolism.