From Gatekeepers to Regenerators: the Plasticity of Paneth Cells.

Paneth cells (PCs) are secretory cells in the small intestine with functions in intestinal homeostasis and innate immunity, with recent studies showing their ability to dedifferentiate and contribute to epithelial regeneration after injury. In this issue of The EMBO Journal, Yang et al, (2026) identify reactive oxygen species (ROS) as a central determinant of PC identity and uncover the Rho-family GTPase CDC42 as a critical regulator of this process. A recent study identifies CDC42 as a regulator of ROS-balance-dependent Paneth cell identity and antimicrobial function.