Reserve intestinal stem cells (rISCs) mediate epithelial regeneration following tissue damage. Unlike active intestinal stem cells (aISCs), rISCs slowly cycle under homeostatic conditions, allowing for their identification with label retention assays. In response to certain epithelial injuries, rISCs convert to an actively dividing state and demonstrate multipotency and self-renewal, which are defining properties of stem cells. Little is known about the genetic mechanisms that regulate the production and maintenance of rISCs.