Mechanistically, methionine is catabolized to S‐adenosyl‐methionine (SAM) to promote the transcription of PCSK9, a key orchestrator of cholesterol metabolism, via DNMT1‐mediated DNA methylation and suppressing SIRT6 expression, leading to the ectopic elevation of PCSK9 in tumor and immunotherapy resistance. The gene discussed is DNMT1; the disease is neoplasm.