SDHAF1 (succinate dehydrogenase complex assembly factor 1) is an essential mitochondrial protein that mediates assembly of succinate dehydrogenase (SDH/Complex II), a critical enzyme linking the tricarboxylic acid cycle and the electron transport chain 1. SDHAF1 specifically promotes maturation of the iron-sulfur protein subunit SDHB by transiently binding to aromatic peptides of SDHB through its C-terminal arginine-rich region and recruiting the iron-sulfur transfer complex (HSC20-HSPA9-ISCU) via its N-terminal LYR motif 2. This assembly function protects SDHB from oxidative damage 3, with SDHAF1 acting cooperatively with SDHAF3 3. Functionally, SDH couples succinate oxidation to fumarate with ubiquinone reduction, ultimately enabling ATP generation through oxidative phosphorylation 1. Pathogenic SDHAF1 mutations cause rare mitochondrial complex II deficiency presenting as infantile leukoencephalopathy with elevated serum and white matter succinate/lactate levels 2. Disease-causing variants impair SDHB binding or iron-sulfur cluster transfer, triggering SDHB degradation 2. Clinical manifestations include Leigh syndrome, cardiomyopathy, developmental delay, and neurological dysfunction 4. Riboflavin treatment ameliorates neurologic symptoms by enhancing SDHA flavinylation and reducing succinate and HIF-1α/2α levels 2. SDHAF1 mutations represent one of four genes (alongside SDHA, SDHB, SDHD) causing isolated complex II deficiency 5.