SDHAF3 (succinate dehydrogenase complex assembly factor 3) is an essential mitochondrial protein that mediates maturation of the iron-sulfur cluster subunit SDHB of succinate dehydrogenase (SDH/respiratory complex II) 1. SDHAF3 functions as a LYR factor that acts together with SDHAF1 to promote SDHB maturation by binding to the Sdh1/Sdh2 intermediate and protecting it from oxidative damage 1. The protein directly interacts with SDHB, with residue 242 being critical for this interaction 2. SDH couples succinate oxidation to fumarate with ubiquinone reduction in both the tricarboxylic acid cycle and mitochondrial electron transport chain. SDHAF3 dysfunction is clinically significant in neuroendocrine tumors. A variant (c.157 T > C, p.Phe53Leu) shows increased prevalence in familial and sporadic pheochromocytoma/paraganglioma (PC/PGL) patients (6.6% vs. 1.2% in normal populations) and exhibits impaired SDHB interaction 2. This variant is hypomorphic, reducing SDH assembly capacity 2. SDHAF3 mutations have been identified in vagal paraganglioma cases, often co-occurring with other SDH gene variants 3. Drosophila lacking SDHAF3 show reduced SDH activity, hypersensitivity to oxidative stress, and muscular/neuronal dysfunction 1. SDHAF3 expression varies tissue-specifically, with particular significance in metabolically active tissues 4.