I looked through the TRS3253E data sheet and didn't see an answer to this question. In the footprint section at the end, it mentions that "the thermal pad can be attached directly to the appropriate copper plane shown in the electrical schematic for the device." However the only schematic symbol in the document leaves out the thermal pad, so it's not clear whether the exposed pad can connect to ground or some other plane, or if it must be left electrically isolated.