CBS (cystathionine beta-synthase) is a key metabolic enzyme that catalyzes the first committed step of the transsulfuration pathway, converting homocysteine to cystathionine 1. The enzyme plays critical roles in hydrogen sulfide (H2S) biosynthesis and cellular protection mechanisms 2. CBS contains characteristic CBS domains that function as sensors of intracellular metabolites, potentially binding adenosine-containing ligands such as ATP, AMP, or S-adenosylmethionine 3. The enzyme requires cofactors including vitamin B6 and heme for optimal function 4. CBS deficiency causes homocystinuria, a genetic disease characterized by thrombosis, mental retardation, and other severe manifestations, though early detection and dietary modification can reduce pathology 4. The enzyme's expression is regulated by hypoxia-inducible factors (HIFs), with chr21 hypoxia increasing CBS mRNA, protein, and catalytic activity in brain tissues as an adaptive response 5. CBS also plays roles in cancer biology, where the ATF3-CBS signaling axis enables colorectal cancer cells to resist ferroptosis, particularly under cystine deprivation conditions 6. Additionally, CBS/H2S signaling enhances cytotrophoblast migration and invasion through mitochondrial regulation, with reduced CBS levels associated with pregnancy complications like pre-eclampsia 2.