CaMKIIδ has been shown to modulate cardiac sarcoplasmic reticulum (SR) Ca²⁺ release via interaction with the ryanodine receptor (RyR2) complex [1]. However, the nature and functional consequences of this interaction remain unclear. CaMKIIδ may interact directly with RyR2 or with accessory proteins that exist as part of the multi-protein channel complex. In this study, we have explored the possibility that CaMKIIδ may interact directly with sorcin and that RyR2 may be modulated via this route. Sorcin is a 22kDa member of the penta EF-hand family of Ca²⁺ binding proteins. It has been shown to negatively modulate RyR2 channel open probability and this is dependent on the phosphorylation status of sorcin [2]. We have examined the possibility of direct CaMKIIδ-sorcin interaction in surface plasmon resonance (SPR) studies, which allow direct protein-protein interactions to be measured in real time. One protein is immobilised on a sensorchip while the other is injected over the chip surface. Protein binding is measured by a change in refractive index expressed as response units (RU). We used recombinant sorcin and CaMKIIδ_C in SPR experiments. The CaMKIIδ_C isoform variant was used since this is the isoform expressed in the cytosol of cardiomyocytes and is involved in regulation of excitation-contraction coupling [3]. Conditions were optimised for CaMKIIδ_C immobilisation. Sorcin (0.3-1μM) and calmodulin (0.3-1μM) were used as analytes. We then explored the nature of the sorcin-CaMKIIδ interaction in more detail by (i) measuring kinase activity in the presence and absence of sorcin and (ii) examining if sorcin may be a substrate for CaMKIIδ. SPR studies suggest that CaMKIIδ and sorcin interact. The CaMKIIδ-sorcin interaction is weaker (10.85±2.05 RU) than the CaMKIIδ-calmodulin interaction (52.98±3.13 RU) (n=4, P=0.00003). It can occur in the presence or absence of calmodulin and is Ca²⁺ dependent. Initial results with recombinant proteins from kinase assays suggest that sorcin affects CaMKIIδ activity. In kinase experiments using a CaMKIIδ-selective peptide substrate, the presence of sorcin (10μM) significantly decreased CaMKIIδ-mediated phosphate incorporation (0.16±0.04 (control) vs 0.02±0.0002 (with sorcin) pmol phosphate incorporated/min/30ng CaMKIIδ, n=3, p<0.05). Evidence is provided for an interaction between sorcin and CaMKIIδ. Sorcin appears to decrease CaMKIIδ activity. Under the assay conditions used, this could either reflect a direct modulation of CaMKIIδ or an ability to act as an alternative substrate. The significance of this interaction remains unclear however it may provide one route by which the CaMKIIδ/RyR2 interaction is modulated. Future experiments will examine the effects of sorcin overexpression on endogenous CaMKIIδ activity in isolated cardiac cells and more specifically, the effects on RyR2 associated kinase and function.