In metazoa, phosphorylation cascades controlling cell cycle progression have been well established to influence membrane trafficking events, particularly at the Golgi apparatus, but also in endocytosis. There is also an accumulating body of knowledge that describes the effects of particular kinases on the secretory and endocytic systems. Clearly phosphorylation, as a universal means of coordinating diverse physiological outputs, plays diverse roles in membrane traffic. We suggest that our study reveals a view of the Rab GTPase Sec4p that incorporates a regulatory phosphorylation mode into the existing cycles of nucleotide binding/hydrolysis and translocation between membranes and cytosol. Future studies are needed to address the timing and spatial contexts of the phosphorylation events as well as the signal transduction network which impinge on these events. Heart failure is one of the most prevalent forms of chronic cardiovascular disease. It accounts for a considerable proportion of death, disability and health care expenditure particularly in individuals over 65 years of age. Pathophysiologically, HF typically represents the end result of myocardial damage in association with cardiomyocyte loss which contributes importantly to progressive ventricular remodelling. Unlike other organs such as the liver and bone marrow, the regenerative capacity of the myocardium is insufficient to mount a substantive regenerative response within the current clinical context. However, with the recognition that a pool of cardiac methylation level specific kind progenitor cells exist in the heart and the potential capacity of cardiomyocytes to proliferate, there has been considerable interest in the development of strategies for exploiting the possibility of cardiac regeneration in the prevention and treatment of HF. Recently, the cardiac surgical resection model in zebrafish and neonatal mice has been successfully exploited to study myocardial regeneration. These studies have demonstrated that in this experimental construct, there exists a regenerative potential within the heart, possibly arising from within the epicardium. Whilst these studies have provided novel insights into the cardiac response to acute injury, the relevance of these studies to HF is limited, as they do not recapitulate the progressive nature of HF. In particular, they also exclude the potential influence of important aspects of the pathophysiology of HF including the presence of cardiomyocyte apoptosis and alterations in the expression profile of neurohormones and cytokines which may modify a potential innate regenerative response. Activation of the sympathetic nervous system is also a pivotal feature of progressive heart failure, and we previously showed that the magnitude of the activation of cardiac sympathetic nerves was strongly associated with the risk of death from heart failure. In conjunction, a key component of the altered sympathetic nervous system pathology is a reduction in sympathetic nerve density, which we have demonstrated to be associated with a reduction in the tissue levels of nerve growth factor both in experimental animals and humans. NGF is a prototypic member of the neurotrophin family, and was initially recognized as a pro-survival and pro-differentiation factor for sensory and sympathetic neurons. Acting via its key cognate receptor it has also recently been demonstrated to exhibit angiogenic activities and pro-survival actions in the setting of acute myocardial ischemic injury.