To investigate a potential relationship between CACNA2D2-associated epilepsy and structural brain changes associated with temporal lobe epilepsy (TLE), we examined hippocampal sections from WT and CACNA2D2 KO mice for patterns of granule cell activity based on the expression of the activity-dependent immediate early genes c-fos and ΔFosB, as well as for a range of other histopathological markers typically associated with TLE. Here, CACNA2D2 is linked to temporal lobe epilepsy.