DCTN2 encodes dynactin subunit 2, a key component of the dynactin complex that activates cytoplasmic dynein for microtubule-based cellular transport. DCTN2 is essential for proper centrosome function and mitotic spindle organization, with abnormal expression linked to centrosome amplification 1. The protein forms complexes with ROCK1 under diabetic conditions, promoting centrosome amplification in colon cancer cells 1. In neurodegenerative diseases, DCTN2 colocalizes with phosphorylated α-synuclein in Lewy bodies characteristic of Parkinson's disease and dementia with Lewy bodies, but not in multiple system atrophy inclusions 2. DCTN2 also interacts with pathological α-synuclein across different disease conditions 3. In cancer, DCTN2 expression is elevated in multiple tumor types including hepatocellular carcinoma, where it promotes tumor progression through AKT pathway activation 4. High DCTN2 expression correlates with poor prognosis and serves as part of prognostic gene signatures in hepatocellular carcinoma 5. While transient overexpression disrupts cellular function, some cancer cells like SJSA-1 can tolerate sustained DCTN2 overexpression despite phenotypic abnormalities 6. These findings establish DCTN2 as a critical regulator of cellular transport with significant roles in neurodegeneration and cancer progression.