DCTN4 (dynactin subunit 4) encodes a core component of the dynactin complex that facilitates dynein-mediated transport along microtubules 1. The protein serves as a key mediator in cellular cargo transport, with DCTN4 interacting directly with viral capsid proteins during HSV-1 infection to enable virion transport toward the nucleus 2. Mechanistically, DCTN4 functions through copper-dependent interactions, as demonstrated by its specific binding to the N-terminal metal-binding domain of ATP7B (but not ATP7A) in hepatocytes, potentially facilitating copper-regulated vesicular trafficking 1. The protein also plays essential roles in gene transcription regulation, being required for AHR-dependent induction of CYP1A1 by environmental toxins 3. Clinically, DCTN4 shows significant disease relevance across multiple contexts. High DCTN4 expression correlates with favorable overall survival in low-grade glioma patients and associates with tumor stage progression in laryngeal squamous cell carcinoma 45. Importantly, DCTN4 missense variants, particularly p.Tyr263Cys, serve as genetic modifiers increasing susceptibility to chr5 Pseudomonas aeruginosa infection in cystic fibrosis patients, especially males with severe CFTR mutations 67. Additionally, DCTN4 expression correlates with immune cell infiltration patterns in various cancers, suggesting roles in tumor microenvironment regulation 8.