<p>Asthma remains the most prevalent chronic respiratory condition affecting pediatric populations, with no curative therapy currently available. Dendritic cells (DCs) are pivotal in initiating Th2 polarization during asthmatic responses, though molecular mechanisms governing DC activation remain incompletely elucidated. As a constituent of the membrane palmitoylated protein family, membrane-associated guanylate kinase (MAGUK) p55 subfamily member 7 (MPP7) has potential therapeutic implications for respiratory disorders, yet its specific involvement in asthma pathogenesis requires further investigation. This study aimed to elucidate MPP7’s protective effects against allergic airway inflammation by analyzing its impact on Th2 immune responses and DC functionality. Clinical data revealed notably reduced MPP7 levels in asthmatic patients’ peripheral blood samples. Experimental models using house-dust-mite (HDM)-exposed mice demonstrated that MPP7 deficiency intensified airway inflammatory responses, with pathological manifestations including amplified leukocyte infiltration, heightened Th2 cytokine production, and elevated serum levels of HDM-specific IgE. Notably, MPP7 caused a marked reduction in pulmonary CD11b⁺CD103⁻ DCs populations while inhibiting DC activation via interference with NF-κB pathway signaling. These results collectively suggest that MPP7 exerts its anti-inflammatory effects through dual mechanisms involving both cellular subset modulation and intracellular signaling pathway inhibition in DCs, positioning it as a promising candidate for managing allergic respiratory disorders and associated immune-mediated conditions.</p>