The role of protein lactylation in skin diseases: from molecular mechanisms to potential therapeutics.

Lactylation represents a novel post-translational modification originating from lactate, a by-product of glycolysis. It has emerged as a pivotal mechanism linking cellular metabolism to epigenetic regulation. By transferring the lactyl group to lysine residues on both histone and non-histone proteins, this modification regulates gene transcription and protein function, thereby coordinating critical biological processes, including metabolic reprogramming and immune-inflammatory responses. Recent studies have highlighted the pivotal role of lactate and lactylation in the pathogenesis of diverse skin diseases, including immune-inflammatory skin diseases (e.g., psoriasis and atopic dermatitis), pathologic scars, skin malignancies (e.g., melanoma), and skin ageing. In certain diseases, such as psoriasis and melanoma, lactylation has been established as a core molecular mechanism, establishing a pathological link between systemic metabolic disorders, the local skin microenvironment, immune inflammatory processes, and skin diseases. In other conditions, lactate-mediated effects have been well documented, while the specific contribution of lactylation remains an active area of investigation. Currently, lactylation-related inhibitors have demonstrated therapeutic potential in cancer, metabolic, and immunological fields. Consequently, lactate-mediated lactylation may emerge as a novel therapeutic intervention target for skin disorders. In this review, we summarize recent advances in lactylation research in skin diseases and elucidate its potential as a therapeutic target for future clinical applications.