MafK, a member of the small Maf family of basic region leucine zipper (bZIP)-type transcription factors, forms homodimers and heterodimers with CNC and Bach proteins [4]. It lacks a transcriptional activation domain and its homodimers act as transcriptional repressors, while its heterodimers can participate in either activation or repression depending on the partner molecules and context. MafK is involved in various biological pathways such as the stress response and detoxification pathways, and has been linked to diseases like ulcerative colitis, diabetes, neuronal disorders, thrombocytopenia, and carcinogenesis [4,6].

MafK overexpressing transgenic mice were more susceptible to Salmonella mucosal infection, with higher mortality, more weight loss, intestinal damage, and inflammation, and unable to control Salmonella colonization and dissemination. This was due to increased caspase-3 activation promoting epithelial cell apoptosis [1]. In non-immune cells, MafK mediates chromatin remodeling to silence IRF8 expression in a cell-type specific manner [2]. In colorectal cancers, MafK is identified as a key transcription factor for the iCMS3 subtype [3]. MafK positively regulates NF-κB activity by enhancing CBP-mediated p65 acetylation [5]. Mice deficient in Mafg and Mafk show misexpression of genes related to cytoskeleton, cell cycle, extracellular matrix and lens developmental defects [7]. β-cell-specific Mafk overexpression in transgenic mice impairs pancreatic endocrine cell development due to reduced β-cell proliferation and altered expression of β-cell-related genes [8].

In conclusion, MafK plays essential roles in transcriptional regulation, influencing various biological processes and disease conditions. Studies using mouse models, including overexpression and knockout models, have revealed its functions in infection, chromatin remodeling, cancer, inflammation, and organ development, providing insights into disease mechanisms and potential therapeutic targets.