This study identifies NSUN2 and YBX1 as the m5C “writer” and “reader” of ENO1 in colorectal cancer, culminating in a positive feedback loop involving the NSUN2/YBX1/m5C‐ENO1 signaling axis, thereby bridging the connection between metabolic reprogramming and epigenetic remodeling. The gene discussed is YBX1; the disease is colorectal cancer.