Trafficking kinesin-binding protein 1 (TRAK1)

Trafficking kinesin-binding protein 1 (TRAK1) is an intracellular adaptor protein essential for microtubule-based mitochondrial trafficking, primarily in neurons. TRAK1 physically links mitochondria to kinesin-1 motors via interaction with Miro proteins, enabling efficient anterograde and retrograde mitochondrial transport along neuronal axons. TRAK1 also interacts with dynein/dynactin for bidirectional movement and is crucial for proper mitochondrial distribution, function, and membrane potential. Disruption of TRAK1 function (by mutation or pathogenic variants) leads to impaired mitochondrial dynamics, neurodegeneration, and severe neurodevelopmental diseases such as developmental and epileptic encephalopathy 68 (DEE68)[1][2][3]. TRAK1 additionally regulates endosome-to-lysosome trafficking, including GABA-A receptor trafficking, and is required for recruiting O-GlcNAc transferase (OGT) to mitochondrial surfaces, influencing mitochondrial motility and potentially cellular metabolism[3]. No drugs target TRAK1 directly, but its dysfunction highlights therapeutic potential in neurological and mitochondrial disorders.

Other names

Protein MiltonKIAA1042OIP106MILT1106 kDa O-GlcNAc transferase-interacting proteinOGT-interacting protein 106 kDaO-linked N-acetylglucosamine transferase interacting protein 106Milton homolog 1 (Drosophila)DEE68EIEE68