Metabolic syndrome is an initial stage to the lifestyle related illnesses cardiovascular disease and diabetes. Metabolic syndrome may be associated with adipocytokine-dependent pro-inflammation. Protein kinase A (PKA) is a regulator of normal immune responses and PKA may modulate normal immune responses through regulation of lymphocyte sensitivity to antigens. In immune tissues, PKA is made up of two regulatory (R) and two catalytic (C) subunits of which one represents a lymphocyte-specific C subunit designated Câ2. Câ2 is equipped with an N-terminal end of 62 amino acids which is unique when compared to any other PKA C subunit. The N-terminal end is shaped as an á-helix which forms a hydrophobic surface between amino acid 18 and 31. Based on other proteins with similar domains it is speculated that the N-terminus may target Câ2 in close proximity to the lymphocyte cell membrane. To regulate pro-inflammatory responses in metabolic syndrome may be accomplished by modulating cAMP effects by displacement of Câ2 from its inhibiting binding partner. To accomplish this, a first step will be to characterise the nature of Câ2 s subcellular localisation by identifying potential Câ2 interaction partner(s). A two-hybrid screen using Câ2 as bait was conducted by Dualsystems Biotech. This revealed a potential interaction partner for Câ2 designated G-patch and KOW containing protein (GPKOW). We could demonstrate that over-expressed GPKOW and Câ2 interact in 293T cells confirming the results from the yeast two-hybrid screen. Moreover, in 293T cells over-expressed GPKOW and Câ2 co-localised in the nucleus of quiescent interphase cells and in cells at M phase in the cell cycle. This was not the case in unstimulated Jurkat cells were GPKOW and Câ2 appeared localised to different cellular compartments, the nucleus and cytosol. Indeed we were unable to co-immuoprecipitate GPKOW and Câ2 from unstimulated Jurkat cells. Finally, we could demonstrate that the interaction between GPKOW and Câ2 probably requires the unique N-terminal end of Câ2, for the first time demonstrating a PKA C subunit splice variant-specific binding protein. The function of the nuclear associated GPKOW is elusive. However, when associated with Câ2, which regulates normal immune responses, GPKOW may be implicated in regulating lymphocyte-specific immune responses in the nucleus.