CTH (cystathionine gamma-lyase) catalyzes the final step of the transsulfuration pathway, cleaving L-cystathionine into L-cysteine, ammonia, and 2-oxobutanoate in a pyridoxal-5'-phosphate-dependent manner 1. Beyond cysteine production, CTH generates the gaseous signaling molecule hydrogen sulfide (H2S) from L-cysteine and L-homocysteine substrates 1. CTH also mediates protein sulfhydration, converting cysteine residues to persulfides on targets like TFEB, regulating their function 2. H2S production by CTH participates in vasodilation, vascular protection, and inflammation regulation 1. In atherosclerosis, CTH-derived H2S activates TFEB-mediated autophagy in vascular smooth muscle cells, promoting collagen secretion and inhibiting apoptosis to stabilize atherosclerotic plaques 2. CTH expression correlates inversely with plaque vulnerability 2. In glioblastoma, CTH is essential for tumor invasion through transsulfuration pathway-mediated redox metabolism; CTH inhibition reduces tumor volume and stemness markers 34. The CTH/H2S axis also regulates abdominal aortic aneurysm development through macrophage ferroptosis 5. CTH gene mutations, including 1364T/T polymorphisms, elevate homocysteine levels, a risk factor for Alzheimer's disease 6. Bioinformatic analyses identify multiple previously unknown CTH mutations in lung adenocarcinoma patients 7. The primary disease association is cystathioninuria, caused by CTH deficiency.