LDHD encodes a mitochondrial D-lactate dehydrogenase that specifically catabolizes D-lactate, preventing its toxic accumulation in the organism 1. The enzyme demonstrates stereoselective activity, targeting D-lactate but not its L-stereoisomer, and converts D-lactate to pyruvate through FAD-dependent oxidation 1. D-lactate originates from endogenous methylglyoxal metabolism, intestinal bacterial activity, and dietary sources 1. Loss-of-function mutations in LDHD cause D-lactic aciduria, characterized by elevated plasma and urinary D-lactate levels 123. Clinical manifestations include developmental delay, cerebellar ataxia, neurological symptoms, and early-onset gout 243. The enzyme's deficiency represents an autosomal recessive disorder with variable phenotypic expression, ranging from isolated hyperuricemia to severe neurological impairment 43. In cancer biology, LDHD plays a protective role against ferroptosis in cancer stem cells by eliminating toxic D-lactate while generating pyruvate for energy metabolism 5. The gene's expression correlates with tumor prognosis, particularly in hepatocellular carcinoma, where it functions as a tumor suppressor by inhibiting proliferation, migration, and invasion through regulation of epithelial-mesenchymal transition pathways 6.