Dctn6, also known as dynactin 6, is a component of the cell dynactin complex involved in dynein-mediated retrograde transport of cargo vesicles [2]. The dynactin complex is crucial for various cellular functions related to intracellular transport, which impacts numerous biological processes at the cellular and organismal levels.

In mice, Dctn6 deficiency enhances the formation of aging-associated dystrophic neurites in the brain. Specifically, Dctn6 interacts with Reticulon 3 (RTN3), and its deficiency leads to increased RTN3 protein levels, high molecular weight RTN3 levels, and hippocampus-specific dystrophic neurite formation in aging transgenic mice overexpressing RTN3. This indicates that the Dctn6-RTN3 interaction is important for tubular ER trafficking in axons, and Dctn6 deficiency impairs axonal ER trafficking, causing abnormal ER accumulation and dystrophic neurite formation [2].

In swine, the structural glycoprotein E2 of classical swine fever virus (CSFV) interacts with Dctn6. A recombinant CSFV mutant with disrupted E2-Dctn6 interaction showed reduced replication in swine cells and decreased virulence in swine, suggesting that the E2-Dctn6 interaction plays a role in CSFV virulence [1].

In cutaneous melanoma and low-grade glioma, high expression of Dctn6 is associated with favorable overall survival, indicating its potential as a prognostic biomarker in these cancers [3,4].

In conclusion, Dctn6 is essential for dynein-mediated retrograde transport. Studies using mouse models and virus-host interaction models have revealed its role in neurodegenerative-like processes in aging mice, viral virulence in swine, and cancer prognosis. These findings highlight the importance of Dctn6 in understanding the mechanisms of these biological processes and diseases.