In colorectal cancer, high expression of SIRT5 regulates the non-oxidative pentose phosphate pathway by activating transketolase (TKT) in a depropionylation-dependent manner, which increases ribulose-5-phosphate (R5P) production and supports nucleotide synthesis, thereby enhancing DNA damage and cell proliferation in CRC 202. Here, SIRT5 is linked to colorectal cancer.