Neuronal calcium sensor (NCS) proteins have multiple key roles in controlling neuronal function in health and disease. In hippocampal neurons the NCS protein VILIP-1 (visinin-like protein 1) shows a fast, stimulus-dependent and reversible translocation to Golgi and cell surface membranes. The calcium-and myristoylation dependent membrane association, the calcium-myristoyl switch of VILIP-1, might provide a fast signalling mechanism to influence membrane-associated signalling effectors. In line with this notion, we have observed effects of VILIP-1 on membrane-localized signalling systems including the nicotinic acetylcholine receptor a4ß2 and the receptor guanylyl cyclase GC-B. In hippocampal neurons both receptors are highly expressed and calcium-dependently co-localize with VILIP-1 as shown by confocal microscopy. The overexpression of VILIP-1 increases the agonist sensitivity of the nAChR in oocytes and the cGMP accumulation following stimulation of GC-B with the agonist C-type natriuretic peptide (CNP) in hippocampal neurons. In order to investigate the molecular mechanisms underlying receptor modulation by VILIP-1, we have examined the influence on cell surface expression and receptor trafficking. We postulate that VILIP-1 is a general modulator of receptor trafficking and, thus, might be involved in hippocampal synaptic plasticity.