Adult intestinal stem cells are essential for maintaining epithelial homeostasis and regeneration. These stem cells reside in specialized niches and are responsible for the continuous renewal of the intestinal epithelium. Recent advances in identifying specific markers for these stem cells, along with new technologies for tracking their activity in vivo and generating new epithelia ex vivo, have significantly improved our understanding of their role in homeostasis, regeneration, and cancer. These insights have the potential to accelerate the development of stem cell-based therapies and improve cancer treatments. Intestinal stem cells are found in the crypt base of the intestinal epithelium, where they self-renew and generate new epithelial cells. The LGR5+ crypt base columnar (CBC) stem cells are a key population of intestinal stem cells, identified by their expression of the LGR5 receptor. These cells are regulated by signals from neighboring cells, including Paneth cells, which provide factors such as EGF, WNT3A, and Notch ligands. The size and activity of the stem cell pool are also regulated by nutrient availability, with calorie restriction reducing mTORC1 signaling and leading to a decrease in the LGR5+ stem cell pool. Recent studies have identified reserve stem cells that can be rapidly recruited to maintain epithelial homeostasis following injury. These cells are distinct from the regular stem cell population and are thought to be located in the +4 position from the crypt base. The +4 model suggests that these cells are relatively quiescent, resistant to acute injury, and capable of retaining DNA labels. However, the identity of these cells remains debated, with some studies suggesting that they may be a distinct population of stem cells. The stem cell zone model proposes that the CBC cells at the base of the crypt are the resident stem cells. These cells are responsible for generating all major epithelial cell lineages and are regulated by signals from neighboring cells. The LGR5+ CBC stem cells have been shown to self-renew and generate organoids in ex vivo culture, confirming their stem cell identity. These cells are also regulated by WNT signaling, which is essential for maintaining epithelial homeostasis. The identification of specific markers for intestinal stem cells, such as LGR5, has enabled the development of new tools for studying their behavior in vivo and ex vivo. These tools have led to a better understanding of how intestinal stem cells interact with their niche to maintain homeostasis and how they may contribute to cancer initiation and progression. The discovery of these markers has also provided insights into the regulation of stem cell activity and the factors that influence their self-renewal and differentiation.Adult intestinal stem cells are essential for maintaining epithelial homeostasis and regeneration. These stem cells reside in specialized niches and are responsible for the continuous renewal of the intestinal epithelium. Recent advances in identifying specific markers for these stem cells, along with new technologies for tracking their activity in vivo and generating new epithelia ex vivo, have significantly improved our understanding of their role in homeostasis, regeneration, and cancer. These insights have the potential to accelerate the development of stem cell-based therapies and improve cancer treatments. Intestinal stem cells are found in the crypt base of the intestinal epithelium, where they self-renew and generate new epithelial cells. The LGR5+ crypt base columnar (CBC) stem cells are a key population of intestinal stem cells, identified by their expression of the LGR5 receptor. These cells are regulated by signals from neighboring cells, including Paneth cells, which provide factors such as EGF, WNT3A, and Notch ligands. The size and activity of the stem cell pool are also regulated by nutrient availability, with calorie restriction reducing mTORC1 signaling and leading to a decrease in the LGR5+ stem cell pool. Recent studies have identified reserve stem cells that can be rapidly recruited to maintain epithelial homeostasis following injury. These cells are distinct from the regular stem cell population and are thought to be located in the +4 position from the crypt base. The +4 model suggests that these cells are relatively quiescent, resistant to acute injury, and capable of retaining DNA labels. However, the identity of these cells remains debated, with some studies suggesting that they may be a distinct population of stem cells. The stem cell zone model proposes that the CBC cells at the base of the crypt are the resident stem cells. These cells are responsible for generating all major epithelial cell lineages and are regulated by signals from neighboring cells. The LGR5+ CBC stem cells have been shown to self-renew and generate organoids in ex vivo culture, confirming their stem cell identity. These cells are also regulated by WNT signaling, which is essential for maintaining epithelial homeostasis. The identification of specific markers for intestinal stem cells, such as LGR5, has enabled the development of new tools for studying their behavior in vivo and ex vivo. These tools have led to a better understanding of how intestinal stem cells interact with their niche to maintain homeostasis and how they may contribute to cancer initiation and progression. The discovery of these markers has also provided insights into the regulation of stem cell activity and the factors that influence their self-renewal and differentiation.