Here, with a battery of histological, electrophysiological, and behavioral experiments we demonstrate for the first time that (i) Trpm4 is present in hilar MC, (ii) plays a role in their intrinsic electrophysiological properties, (iii) contributes to MC death following status epilepticus (SE) and therefore (iv) modulates seizure susceptibility, and (v) epilepsy-related memory deficits in the chronic phase of experimental TLE. Here, TRPM4 is linked to epilepsy.