SARDH (sarcosine dehydrogenase) is a mitochondrial flavoenzyme that catalyzes the final oxidative degradation step of choline to glycine, specifically converting sarcosine to glycine 1. The enzyme contains a covalently bound FAD cofactor and is primarily expressed in liver, with significant presence in lung, pancreas, kidney, thymus, and oviduct 1. SARDH functions as a critical regulator of one-carbon metabolism, with emerging evidence indicating tumor suppressor activity 2. Loss of SARDH leads to sarcosine accumulation and reduced S-adenosylmethionine (SAM) consumption, impairing epigenetic regulation and T-cell function 3. SARDH alterations are associated with multiple cancer types; deleterious mutations occur in colorectal cancer, and decreased expression correlates with enhanced cellular invasion and proliferation 24. In breast cancer, SARDH expression varies by subtype, with lowest expression in triple-negative breast cancer 5. Genetic deficiency of SARDH causes sarcosinemia, an amino acid metabolism disorder in humans 1. Targeting SARDH represents a potential cancer therapeutic strategy through modulation of T-cell metabolism and one-carbon pathway regulation 3.