YBX1 (Y-box binding protein 1) is a multifunctional nucleic acid-binding protein that operates primarily as an RNA-binding protein with diverse roles in gene regulation. As an m5C reader, YBX1 recognizes 5-methylcytosine-modified mRNAs and recruits ELAVL1 to stabilize target transcripts 1, a mechanism exploited in multiple cancer contexts. In esophageal squamous cell carcinoma, YBX1 stabilizes SMOX mRNA in m5C-dependent manner, activating mTORC1 signaling and promoting tumor progression 2. Similarly, in EGFR-mutant non-small-cell lung cancer, the NSUN2/YBX1 axis mediates gefitinib resistance by stabilizing QSOX1 translation 3. YBX1 also regulates glucose metabolism reprogramming in colorectal cancer through m5C-ENO1 recognition 4 and promotes perineural invasion in pancreatic cancer when stabilized by PIAT-mediated inhibition of Nedd4l-dependent ubiquitination 5. Beyond m5C recognition, YBX1 functions as a splicing factor regulating alternative splicing events critical for bone marrow stromal cell differentiation during aging 6, and controls leukemia stem cell homing via TSPAN13 mRNA stabilization 7. YBX1 knockdown blocks intrahepatic cholangiocarcinoma progression 8, establishing it as a driver of multiple malignancies through coordinated control of mRNA stability and splicing.