BCKDK, known as branched-chain ketoacid dehydrogenase kinase, plays a crucial role in regulating the activity of the branched-chain α-keto acid dehydrogenase complex. This complex is involved in the catabolism of branched-chain amino acids (BCAAs), which are essential for energy and protein metabolism. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been valuable in studying BCKDK's functions [1,2].

In a muscle-specific Bckdk-cKO mouse model, cancer cachexia was accelerated, with skeletal muscle wasting characterized by increased protein ubiquitination degradation and impaired protein synthesis, indicating that BCKDK-mediated BCAA metabolism is important in preventing muscle atrophy during cancer cachexia [2]. In Parkinson's disease models, downregulation of BCKDK in dopaminergic neurons led to mitochondrial dysfunction, including reduced membrane potential and increased ROS production, promoting α-synuclein oligomerization. BCKDK interacted with the NDUFS1 subunit of Complex I, and its loss disrupted this interaction, destabilizing Complex I and enhancing α-synuclein aggregation [3].

In conclusion, BCKDK is essential for the regulation of BCAA metabolism and mitochondrial function. Model-based research, especially KO and CKO mouse models, has revealed its significance in disease conditions such as cancer cachexia and Parkinson's disease. Understanding BCKDK's functions provides potential targets for treating these diseases.