DLST (dihydrolipoamide S-succinyltransferase) encodes the E2 component of the α-ketoglutarate dehydrogenase complex (KGDHC), which catalyzes the irreversible conversion of α-ketoglutarate to succinyl-CoA in the tricarboxylic acid cycle 1. DLST primarily functions in mitochondrial metabolism, where it governs glutamine entry into the TCA cycle and produces NADH for oxidative phosphorylation 1. The protein also localizes to the nucleus where it provides succinyl-CoA for histone succinylation. DLST demonstrates significant disease relevance across multiple pathological contexts. In neuroblastoma, elevated DLST expression predicts poor outcomes and promotes tumor aggression by enhancing oxidative phosphorylation, making OXPHOS inhibition a potential therapeutic target 1. In inflammatory bowel disease, DLST deficiency reduces FOXP3 succinylation in regulatory T cells, leading to FOXP3 degradation and severe gut inflammation 2. DLST is also subject to pathological modifications, including succination during complex I deficiency, which impairs KGDHC activity and exacerbates mitochondrial ATP deficits 3. The protein plays roles in cuproptosis, a copper-induced cell death pathway, and its expression correlates with disease outcomes in colorectal cancer and periodontitis 45. Additionally, DLST stability can be modulated by lncRNAs, affecting drug resistance in lung adenocarcinoma 6.