Progressive liver fibrosis and resultant cirrhosis is the primary cause of chronic liver failure. Hepatic stellate cells are critically important mediators of liver fibrosis. In the healthy liver, hepatic stellate cells are quiescent lipid-storing cells limited to the peri-sinusoidal endothelium. However, in the injured liver, hepatic stellate cells undergo myofibroblastic transdifferentiation (activation), which is a critical step in the development of organ fibrosis. Hepatic stellate cells express P2Y receptors linking extracellular ATP to inositol trisphosphate-mediated cytosolic calcium signals. Here we report that HSC express only the Type I inositol trisphosphate receptor and that the receptor shifts into the nucleus and cell extensions upon activation. These cell extensions furthermore express sufficient machinery to enable local application of ATP to evoke highly localized calcium signals that induce localized contractions. These autonomous units of subcellular signaling and response reveal a new level of subcellular organization, which in turn establishes a novel paradigm for local control of fibrogenesis in the liver.