MAFB in immunity and disease: An evidence-graded perspective on context-dependent immune regulation.

MAFB is a large Maf family bZIP transcription factor involved in myeloid differentiation, macrophage-state regulation, inflammatory control, and tissue adaptation. Accumulating evidence indicates that MAFB biology is highly context dependent rather than uniformly anti-inflammatory, pro-inflammatory, protective, or pathogenic. In macrophages and related myeloid cells, MAFB has been linked to inflammasome regulation, lipid-mediator switching, efferocytosis, tissue repair, and cell-state transitions. Across diseases, its interpretation depends on cellular source, disease stage, tissue niche, perturbation evidence, and human validation. In sterile inflammatory or repair-associated contexts, MAFB may support inflammatory restraint and resolution-associated programs, whereas in tuberculosis, tumor-associated macrophages, selected malignant cells, and Mendelian renal-skeletal disorders, MAFB-related findings reflect distinct evidence categories and levels of translational maturity. Clinically, current evidence does not support MAFB as a universal biomarker or broadly actionable therapeutic target. Instead, any translational value of MAFB requires interpretation within defined cell types, disease stages, tissue niches, and evidence categories. This review distinguishes direct mechanistic evidence, human genetic or Mendelian causal evidence, animal disease-model evidence, in vitro perturbation data, human tissue, single-cell or spatial association, and author-derived conceptual synthesis. We propose that MAFB is best viewed as a context-dependent immune-regulatory factor whose clinical relevance remains disease- and cell-state-specific and, in many settings, hypothesis-generating. This review highlights evidence boundaries, translational readiness, and priorities for cell-state-specific validation of MAFB biology.