The rate-limiting enzyme of de novo serine synthesis is 3-phosphoglycerate dehydrogenase (PHGDH), of which the copy number is reported to be significantly increased in melanoma to ensure tumor cell survival and proliferation under low physiological serine concentrations.241,242 Supplement of dietary serine or genetic overexpression of PHGDH can efficiently foster melanoma progression via the enhancement of intracellular serine level.242 More intriguingly, PHGDH is also decisive in mediating melanoma metastasis to the brain. The gene discussed is PHGDH; the disease is melanoma.