Echs1, encoding short-chain enoyl-CoA hydratase (SCEH), is a mitochondrial enzyme. It is crucial for fatty acid β-oxidation, playing a key role in the hydration process of this pathway. Additionally, it is involved in valine catabolism. Dysfunction of Echs1 can lead to severe mitochondrial-related disorders, highlighting its biological importance. Genetic models, such as gene knockout mouse models, can be valuable for studying its function [2,3,4,6,7,8].

In colorectal cancer, gain-and loss-of-function analyses have demonstrated that Echs1 promotes cell proliferation, migration, and invasion in vitro and in vivo. It does so 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 patients with Echs1 deficiency, a severe Leigh or Leigh-like Syndrome phenotype can occur, with symptoms including severe developmental delays, regression, dystonia/hypotonia, and movement disorders. The disease has a wide phenotypic spectrum, and patients may present with polymorphic symptoms such as failure to thrive, global developmental delay/regression, movement disorders, ocular abnormalities, hearing loss, seizure, and cardiac myopathy [2,3,5].

In conclusion, Echs1 is essential for fatty acid β-oxidation and valine catabolism. Through model-based research, its role in promoting colorectal cancer progression and causing severe mitochondrial encephalopathy-related diseases has been revealed. Understanding Echs1 function in these contexts may offer potential therapeutic targets for related diseases.