MAPK13

Mitogen-activated protein kinase 13 (MAPK13), also known as p38δ, is a member of the p38 MAPK subfamily that mediates cellular responses to stress and inflammatory stimuli^[1][2]. MAPK13 regulates key biochemical pathways, including the serine synthesis pathway (SSP) via phosphorylation of phosphoglycerate dehydrogenase (PHGDH), leading to its degradation through chaperone-mediated autophagy, thereby modulating redox balance and cellular metabolism under liver injury conditions^[3]. Mechanistically, MAPK13 contributes to IL-13-induced mucus production in airway epithelial cells by activating downstream transcriptional programs^[4]. In immune regulation, MAPK13 phosphorylates transcription factor TCF1, promoting stem-like T-cell expansion and enhancing antitumor immunity in tumor microenvironments^[5][6]. Compared with related p38 isoforms MAPK11, MAPK12, and MAPK14, MAPK13 exhibits distinct tissue-specific expression, epigenetic regulation, and substrate selectivity, which underlies its unique involvement in cellular metabolism, airway inflammation, and T-cell stemness^[1][3][5]. Pathophysiologically, MAPK13 is implicated in drug-induced liver injury, cholestatic liver injury, chronic allograft vasculopathy, airway inflammatory diseases, diabetic wound healing, and cancer progression, where its inhibition or modulation has demonstrated protective or therapeutic potential^[3][5][7][8]. Small molecule inhibitors targeting MAPK13 have been developed to reduce mucus overproduction and enhance rapamycin efficacy in cancer cells, highlighting its relevance for experimental and translational applications^[4][8]. Collectively, MAPK13 serves as a critical stress-responsive kinase with isoform-specific functions, making it a valuable target for research in metabolism, inflammation, and immune regulation^[1][3][5][8].