摘要Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune re-sponses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanisti-cally,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated pre-dominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.