Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded poly-glutamine stretch in the Huntingtin protein (Htt). HD animal models show decreased dense-core vesicle (DCV) secretion, and HD patients feature symptoms associated with altered neuropeptide signaling. However, Htt biological functions and the basic mechanisms by which mutated Htt (mHtt) affects the regulated-secretory pathway remain unclear. In alignment with evidence suggesting a role of Htt in vesicle trafficking, we analyzed DCV mobility in chromaffin cells, a well-known cellular system for neurosecretion. Using confocal imaging and bioimage analysis tools, we previously reported that Htt and mHtt overexpression modified DCV transport regimes, showing an increase in motility and in confined motion, respectively. To study this further, we evaluated DCV mobility across the cell to map DCV motion at defined regions at different distances from the plasma membrane. Spatial analysis of control cells revealed differential distribution of DCV specific motion, with an increase in motility near cell periphery upon K+ stimulation. Htt overexpression also increased peripheral DCV motility, but did not increase it further upon stimulation. Finally, mHtt expression did not affect DCV motility at the periphery but increased immobile and caged DCV inside the cell. This data contributes to our understanding of Htt biology, showing the importance of Htt activity along the DCV trafficking pathway