SORD (sorbitol dehydrogenase) is a polyol dehydrogenase that catalyzes the NAD(+)-dependent oxidation of sorbitol to fructose, serving as a key enzyme in the polyol pathway for glucose metabolism 1. The enzyme acts on multiple sugar alcohol substrates including D-sorbitol, xylitol, and ribitol, converting them to their C2-oxidized products [UniProt via abstracts]. SORD has clinical significance as biallelic mutations in SORD represent the most frequent autosomal recessive form of hereditary distal motor neuropathy (dHMN) 12. Loss-of-function mutations cause accumulation of intracellular sorbitol and elevated serum sorbitol levels in patients, with Drosophila studies demonstrating that SORD loss leads to synaptic degeneration and motor impairment 1. Critically, aldose reductase inhibitors normalize sorbitol levels and ameliorate motor phenotypes, establishing SORD-related neuropathy as potentially treatable 1. The polyol pathway dysfunction in SORD mutations mirrors pathomechanisms implicated in diabetic neuropathy, linking this gene to metabolic complications of hyperglycemia 1. Additionally, SORD participates in glucose/fructose metabolism relevant to cancer progression, with emerging evidence suggesting polyol pathway activation affects cancer cell metastasis 3. Current clinical trials (CMT-SORD trial) are investigating govorestat as a therapeutic option 4.