Mechanistically, NOP2 stimulated m5C modification of apolipoprotein L1 (APOL1) mRNA, and the m5C reader YBX1 stabilized APOL1 mRNA through recognizing and binding to the m5C site in 3′-untranslated regions, which subsequently affected ccRCC progression via the PI3K-Akt signaling pathway. Here, NOP2 is linked to nonpapillary renal cell carcinoma.