Dorsal root ganglion (DRG) neurons are quintessential for peripheral pain transduction, a process mediated, among others, by certain members of the transient receptor potential (TRP) superfamily of ion channels. Among those, TRPA1, TRPV1, TRPM3 and TRPM8 have been linked to chronic pain and neuropathies. Tumor suppressor candidate 5 (Tusc5) plays a role in adipocyte function, but is also expressed in all major classes of DRG neurons. Tusc5 function in DRGs has not been investigated. We conducted Fura-2 calcium imaging and patch clamp experiments in cultured DRG neurons from knock-in Tusc5eGFP male and female mice before and after high fat diet. The neurons were challenged with selective agonists for the aforementioned TRP channels. The agonist-induced calcium transients were quantified and the responses were compared between genotypes and between Tusc5 positive and negative cells from the same animal. Using the patch clamp technique in the current clamp configuration, the parameters of individual action potentials and neuronal firing frequency were analyzed. We find that, upon stimulation with specific agonists Tusc5+TRPM8+ DRGs have significantly lower responses compared to Tusc5-TRPM8+ DRGs, while Tusc5+TRPA1+ DRGs have significantly higher responses compared to Tusc5-TRPA1+ DRGs, regardless of whether one (Tusc5 heterozygote) or both (Tusc5 knockout) copies of Tusc5 have been replaced with eGFP. Patch clamp physiology data indicates that genetic Tusc5 ablation induces a slight, but significant reduction in the amplitude of action potential afterhyperpolarization. Our results suggest that Tusc5 defines subclasses of TRP+ neurons, and may modulate their electrophysiological properties.