Alteration of the cytoskeleton in response to growth factors and extracellular matrix proteins is necessary for neurite growth. The cytoskeletal components, such as actin and tubulin, can be modified through interaction with other cellular proteins, including the small heat shock protein Hsp27. Our previous work suggested that Hsp27 influences neurite growth, potentially via its phosphorylation state interactions with actin. To investigate further the role of Hsp27 in neurite outgrowth of adult dorsal root ganglion (DRG) neurons, we have both down-regulated endogenous Hsp27 and expressed exogenous Hsp27. Down-regulation of Hsp27 with Hsp27 siRNA resulted in a decrease of neuritic tree length and complexity. In contrast, expression of exogenous Hsp27 in these neurons resulted in an increase in neuritic tree length and branching. Collectively, these results demonstrate that Hsp27 may play a role in neuritic growth via modulation of the actin cytoskeleton.