Recent research suggests that certain MSS tumors may acquire MSI‐like features through EGFR/BRAF inhibition.[52] In this study, we propose a novel combination therapy using PRMT5i and CPT‐11, which enhances anti‐tumor immunity by leveraging epigenetic modifications that mediate PMS2 deficiency in MSS CRC. The gene discussed is EGFR; the disease is Marinesco-Sjogren syndrome.