ECHDC1 (ethylmalonyl-CoA decarboxylase 1) is a metabolite proofreading enzyme that decarboxylates ethylmalonyl-CoA, a potentially toxic metabolite, to form butyryl-CoA 1. The enzyme acts preferentially on (S)-ethylmalonyl-CoA and also exhibits lower-level methylmalonyl-CoA decarboxylase activity, but does not act on malonyl-CoA 1. ECHDC1 is particularly abundant in brown adipose tissue, liver, and kidney, and is essentially cytosolic in localization 1. Mechanistically, ECHDC1 functions to correct side activities of acetyl-CoA carboxylase and propionyl-CoA carboxylase, which produce ethylmalonyl-CoA at low rates from butyryl-CoA 1. Loss-of-function variants in ECHDC1 have been identified in humans with elevated ethylmalonic acid levels, suggesting clinical relevance in ethylmalonic aciduria 2. The gene shows disease associations across multiple contexts: it functions as a tumor suppressor in breast cancer 3, its overexpression correlates with gemcitabine resistance in bladder cancer 4, and increased expression is associated with non-alcoholic fatty liver disease through regulation of lipid metabolism 5. Additionally, ECHDC1 has been implicated in cholesterol metabolism regulation 6.