The neuronal calcium sensor family of Ca²⁺-binding proteins are expressed predominantly or only in neurons (Burgoyne & Wiess, 2001). They possess EF-hand motifs and are almost all are N-terminally myristoylated. The different members of the family show varying affinities for free Ca²⁺, suggesting that they may have similar or distinct physiological functions that are determined by the level of free Ca²⁺. It is likely that they play important roles in the regulation of neuronal function. Some significant roles have been identified. For example, NCS-1 is involved in the control of neurotransmitter release (McFerran et al. 1998), Ca²⁺ channel function (Weiss et al. 2000) and learning and memory (Gomez et al. 2001). The KChIP proteins regulate A-type potassium channels (An et al. 2000). In general, however, much is still to be learnt about their cellular functions and in particular the molecular basis for their actions. We have developed a dominant negative mutant of NCS-1 that has allowed us to probe the role of NCS-1 in Ca²⁺ channel regulation (Weiss et al. 2000; Weiss & Burgoyne, 2001). The use of the N-terminal myristoylation for reversible or permanent membrane association of the NCS proteins has been probed in live cells using fluorescent tagged forms of NCS-1 and hippocalcin (O’Callaghan et al. 2002) and also KChIP1. To further address their function, we have developed a method for the isolation of proteins that interact with the NCS proteins in a calcium-dependent manner and tested the feasibility of the approach for one family member known as neurocalcin δ (Ivings et al. 2002). Binding proteins were identified by gel electrophoresis and MALDI-TOF analysis and included clathrin heavy chain, actin, and tubulin (Ivings et al. 2002). These interactions were confirmed using independent assays.