Echs1, short for enoyl-CoA hydratase, short chain 1, is a mitochondrial enzyme. It is a key component in β-oxidation, mediating the hydration process of mitochondrial fatty acid β-oxidation. Echs1 is also involved in the catabolic pathways of isoleucine, valine, and lysine [2,4,5]. It has significant biological importance as its normal function is crucial for energy production and amino acid metabolism in cells. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, can be valuable tools to study its function.

In colorectal cancer, gain-and loss-of-function analyses showed that Echs1 promotes cell proliferation, migration, and invasion both in vitro and in vivo. It does this by inducing sphingolipid-metabolism imbalance, increasing glycosphingolipid synthesis, releasing reactive oxygen species (ROS), and interfering with mitochondrial membrane potential via the PI3K/Akt/mTOR-dependent signaling pathway [1]. In Echs1-deficient patients, it leads to a severe Leigh or Leigh-like Syndrome phenotype, characterized by psychomotor development delay, lactic acidosis, and basal ganglia lesions. Echs1 deficiency can also cause metabolic encephalopathy with a wide range of clinical presentations, which can be grouped into four main phenotypes based on clinical and neuroradiological features [2,3,4].

In conclusion, Echs1 is essential for mitochondrial fatty acid oxidation and amino acid catabolism. Model-based research, especially loss-of-function experiments, has revealed its role in colorectal cancer progression and in causing severe neurological syndromes associated with Echs1 deficiency. Understanding Echs1's functions provides insights into cancer development and certain metabolic encephalopathies, potentially guiding the development of new therapies.