SUCLG2 (succinate-CoA ligase GDP-forming subunit beta) is a mitochondrial enzyme that catalyzes substrate-level phosphorylation in the tricarboxylic acid (TCA) cycle, coupling succinyl-CoA hydrolysis to GTP synthesis 1. The beta subunit provides nucleotide specificity and binds substrate succinate, while the alpha subunit contains coenzyme A and phosphate binding sites 1. Beyond its canonical TCA cycle function, SUCLG2 regulates cellular succinylation patterns; SUCLG2 deficiency increases mitochondrial protein succinylation, dampening metabolic enzyme activity 2. This modified enzyme affects diverse pathologies: SUCLG2 suppression in rheumatoid arthritis T cells shifts the TCA cycle toward reductive metabolism, accumulating acetyl-CoA that drives pathogenic tubulin acetylation and tissue invasion 3. In cancer, SUCLG2 undergoes lysine 93 succinylation, enhancing its stability and promoting lung adenocarcinoma proliferation 2, while circPSD3-mediated SUCLG2 upregulation sustains thyroid carcinoma TCA cycle activity and mitochondrial function 4. Germline SUCLG2 variants impair complex II assembly and SDH function in pheochromocytoma/paraganglioma 5. Additionally, pathogenic TcdB toxin suppresses SUCLG2 to enhance macrophage CD44 succinylation and inflammation 6. SUCLG2 shows cell-type-restricted expression, localized to neurons and vasculature but absent from glial cells in human brain 7.