Given that histone lactylation is dependent on the presence of a substrate produced by glycolysis and considering our finding that NSUN2‐mediated m5C modification leads to the reprogramming of glucose metabolism by targeting ENO1, it seems plausible that an interesting positive feedback loop might exist between histone H3K18la and m5C‐mediated regulation of glycolysis that tandems the epigenetic switch/metabolic reprogramming in CRC progression. Here, ENO1 is linked to colorectal carcinoma.