Cth, also known as cystathionine-γ-lyase, is one of the main enzymes responsible for endogenous hydrogen sulfide (H2S) production. H2S is an endogenous gaseous signaling molecule involved in multiple biological processes. Cth functions in the transsulfuration pathway, where it converts cystathionine to cysteine. It has importance in various physiological and pathological conditions, and genetic models like KO mouse models are valuable for studying its functions [1-10].

In glioblastoma, genetic ablation of Cth in host mice led to a significant reduction in tumor volume and the protumorigenic and stemness transcription factor SOX2, suggesting that Cth inhibition could be a new target against glioblastoma formation [1].

In the context of intestinal ischaemia-reperfusion injury, Cth-ERK1/2-dependent mechanism induced macrophage efferocytosis, which was indispensable for repairing and maintaining intestinal barrier function, as overexpression/silencing of Cth promoted/inhibited the ERK1/2 pathway respectively, affecting efferocytosis and intestinal barrier recovery [2].

In atherosclerotic plaque stability, deletion of Cth in vascular smooth muscle cells (VSMCs) exacerbated plaque vulnerability, associated with VSMC autophagy decline, and these effects were rescued by H2S donor, indicating that Cth-H2S increases VSMC autophagy, promotes collagen secretion and inhibits apoptosis, thereby attenuating atherogenesis and plaque vulnerability [3].

In conclusion, Cth plays essential roles in various biological processes and disease conditions. Studies using gene knockout models, especially in glioblastoma, intestinal ischaemia-reperfusion injury, and atherosclerosis, have revealed its significance in tumorigenesis, intestinal barrier repair, and atherosclerotic plaque stability. Understanding Cth's functions can potentially lead to new therapeutic strategies for these diseases.