ASNS (asparagine synthetase) is a ligase enzyme catalyzing L-asparagine biosynthesis from glutamine and aspartate, primarily localized to the cytosol 1. The enzyme plays critical roles in cellular survival under amino acid starvation, including glucose deprivation responses [GO Annotations]. ASNS expression is transcriptionally regulated by multiple factors including ATF4 and ZBTB1 under nutrient stress conditions 21. Beyond basal metabolic function, ASNS exhibits significant oncogenic properties across multiple cancer types. Elevated ASNS expression and asparagine biosynthesis promote tumor progression in osteosarcoma, breast cancer brain metastasis, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma through metabolic reprogramming pathways 3145. ASNS upregulation represents an adaptive escape mechanism enabling tumor cells to circumvent glutamine metabolism inhibition and asparaginase therapy 56. Clinically, ASNS hypermethylation in gastric and hepatic cancers sensitizes cells to asparaginase therapy, suggesting methylation status as a predictive biomarker 7. Germline ASNS mutations cause asparagine synthetase deficiency associated with severe neurological phenotypes including congenital microcephaly and progressive cerebral atrophy [Disease Associations]. The gene's dual role in normal amino acid metabolism and cancer-associated metabolic reprogramming positions ASNS as both a therapeutic target and potential biomarker in cancer treatment.