CARS2 encodes a mitochondrial cysteinyl-tRNA synthetase with dual functions in protein synthesis and cellular signaling. Beyond its canonical role in aminoacylation, CARS2 exhibits cysteine persulfide synthase activity, producing reactive persulfide species such as cysteine persulfide (CysSSH) that are incorporated into proteins during translation 1. These persulfide modifications serve as potent antioxidants and cellular protectants 1. CARS2 participates in hydrogen sulfide metabolism alongside other enzymes like CBS, CSE, and 3-MST 2. The enzyme plays critical roles in immune regulation and inflammation control. CARS2 expression increases in anti-inflammatory M2 macrophages and decreases in pro-inflammatory M1 macrophages 3. Knockdown studies reveal that CARS2 enhances IL-10 anti-inflammatory signaling through STAT3 phosphorylation and suppresses pro-inflammatory cytokine production 3. In T cell biology, CARS2-dependent supersulfide metabolism restrains CD4+ T cell proliferation, with Cars2+/- mice showing spontaneous accumulation of effector/memory CD4+ T cells and enhanced susceptibility to colitis 4. CARS2 downregulation is associated with inflammatory bowel disease pathogenesis in humans 4. The gene is also implicated in cancer biology, where elevated CARS2 expression supports basal-like breast cancer progression through persulfide-mediated cellular protection 1, and serves as a potential biomarker in osteoarthritis 5.