ADH1C (alcohol dehydrogenase 1C) is a class I alcohol dehydrogenase enzyme primarily involved in ethanol catabolism, catalyzing the NAD+-dependent oxidation of ethanol to acetaldehyde 1. The enzyme exhibits high activity for ethanol oxidation and contains zinc-binding domains essential for catalytic function 2. Beyond its canonical role in alcohol metabolism, ADH1C functions in retinol metabolism and retinoic acid homeostasis. Notably, recent proteomic studies reveal a non-enzymatic function where ADH1C interacts with splicing factor RP9 to enhance PPARα pre-mRNA splicing, promoting fatty acid degradation and reducing hepatic lipid accumulation 3. Genetically, ADH1C variants significantly influence alcoholism susceptibility and alcohol-related disease risk. The ADH1C Ile350Val polymorphism shows strong association with alcohol dependence and abuse, particularly in Asian populations (OR 2.14), with the Ile allele conferring protective effects 2. Similarly, the ADH1C*1 allele reduces head and neck cancer risk by accelerating ethanol metabolism 4. Clinically, ADH1C emerges as a favorable prognostic factor in hepatocellular carcinoma, particularly steatotic HCC, where downregulation promotes tumor cell proliferation and motility 35. ADH1C is also identified in transcriptomic signatures for pancreatic cancer prognosis and triple-negative breast cancer metabolism 67.