Treatment with anti-NKG2D antibodies effectively mitigated disease progression by reducing collagen deposition while suppressing the downstream expression of SYK and p21.<h4>Conclusion</h4>This study proposes that the NKG2D-DAP12-SYK-p53-p21 axis may represent a novel pathogenic pathway in PF, potentially linking immune dysregulation to cellular senescence. The gene discussed is TYROBP; the disease is pemphigus foliaceus.