SDHAF2 (succinate dehydrogenase complex assembly factor 2) is an essential assembly factor required for the functional maturation of succinate dehydrogenase (SDH/complex II), a critical enzyme linking the tricarboxylic acid cycle and mitochondrial electron transport chain 1. SDHAF2 specifically facilitates flavinylation—the covalent attachment of flavin adenine dinucleotide (FAD)—to the SDHA flavoprotein subunit, working synergistically with dicarboxylate cofactors to properly orient the flavin and active site domains 1. This assembly function is vital for complex II-mediated electron transfer from succinate to ubiquinone and coupled oxidative phosphorylation. At the cellular level, SDHAF2-dependent complex II assembly is regulated by mitochondrial morphology; Drp1-controlled mitochondrial fission is necessary for optimal SDHAF2 translocation and complex II assembly, with dysfunction impairing fatty acid oxidation and insulin sensitivity 2. Clinically, SDHAF2 mutations are associated with hereditary pheochromocytoma/paraganglioma syndrome 2 (PGL2), though mutations are rare, occurring in approximately 0.1% of sporadic cases 3. SDHAF2-mutant carriers exhibit distinctive phenotypes including early-onset head and neck paragangliomas with high multifocality and maternal imprinting, requiring distinct surveillance strategies 4. Current guidelines recommend SDHAF2 genetic testing in young patients with isolated head and neck paragangliomas lacking mutations in other susceptibility genes 5.