The putative protein CACHD1 was identified following a systematic search for novel ligand-binding proteins (Anantharaman & Aravind, 2000). CACHD1 has a predicted structure similar to that of the α2δ family of voltage-dependent calcium channel (VDCC) auxiliary subunits. The α2δ subunit isoforms are known to increase membrane expression and modulate the biophysical properties of VDCCs (Davies et al., 2007). Moreover, the α2δ-1 subunit is a binding protein of the anti-epileptic drug gabapentin, also commonly used in neuropathic pain therapy (Hendrich et al., 2008). Here, we examined the expression of CACHD1 within different tissues and tested if CACHD1 functionally interacts with VDCCs by comparing electrophysiological actions of CACHD1 with those of α2δ-1 on the CaV2.2 subunit. Quantitative PCR of CACHD1 and α2δ-1 mRNA was performed on hippocampus, cortex, thalamus, cerebellum, dorsal root ganglia (DRG) and superior cervical ganglia (SCG) tissue from adult Wistar rats. Data were normalised to HPRT1 and expressed as fold difference between average tissue expression (n=3, means±S.E.M., statistical analysis by ANOVA and Tukey post-hoc test). Immunocytochemistry (ICC) was performed on tsA201 cells transiently transfected with CACHD1, using rabbit anti-CACHD1 (1:250) and Alexa 488 IgG (1:1000) antibodies. Whole-cell patch clamp recordings were performed on tsA201 cells transiently transfected with Cav2.2/β2a/GFP with or without α2δ-1 or CACHD1. CACHD1 mRNA levels were significantly higher in the thalamus compared to cortex, DRG and SCG (3.7±0.46, 0.47±0.13, 0.33±0.03 fold, respectively, both p<0.01). α2δ-1 mRNA was significantly higher in the cortex compared to thalamus, cerebellum and DRG (2.13±0.32, 0.51±0.11, 0.19±0.05 and 0.39±0.02 fold, respectively, each p<0.001). ICC showed CACHD1 protein expression at or near the membrane of transiently transfected tsA201 cells. Whole-cell patch clamp confirmed that α2δ-1 co-transfection with Cav2.2/β2a/GFP significantly increase Ca2+ current amplitude (from -24.1±4.6 pA/pF to -70.9±11.1 pA/pF, p<0.0001, n=14-17). However, when CACHD1 was co-transfected with Cav2.2/β2a/GFP, Ca2+ currents amplitude remained unchanged (-23.5±4.7 pA/pF and -24.1±4.6 pA/pF, n=14-17, respectively) and other measured biophysical properties were also unaltered. Results indicate that CACHD1 protein may have a differential, predominantly thalamic, expression within the CNS; such expression is largely complementary to that of α2δ-1. CACHD1 protein may be expressed at the membrane; however, initial data suggests that, unlike α2δ-1, CACHD1 protein does not functionally modulate electrophysiological properties of Cav2.2 channels. In the future, it will be of interest to investigate potential functional effects of CACHD1 on proteins, in particular other VDCCs, expressed at high levels within the thalamus.