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