SHMT2 and neoplasm: SIRT5, a crucial mitochondrial deacetylase, influences tumor metabolism and progression by regulating protein posttranslational modifications such as desuccinylation, demalonylation, and deglutarylation.298 In colorectal cancer, SIRT5 promotes tumorigenesis by enhancing glutaminolytic metabolism.299 SIRT5 can regulate key mitochondrial metabolic enzymes such as malic enzyme 2 (ME2) and SHMT2 through desuccinylation, promoting tumor cell proliferation.300,301 In AML, SIRT5 is critical for maintaining mitochondrial OXPHOS, preserving redox balance, and driving glutaminolysis.302