Akin to the plasticity of Lgr5− disseminated cancer cells that can replenish the damaged Lgr5+ CSC pool [9,286,297,299] and seed Lgr5+ liver metastases [302], a subset of L1CAMlo cells can re-express L1CAM and engage the regenerative gene expression program during chemotherapy, organoid formation, and DSS-induced regeneration [166]. The gene discussed is LGR5; the disease is cancer.