Bcl2l1, also known as Bcl-XL, belongs to the Bcl-2 family. It is a major anti-apoptotic protein. The apoptosis of cells regulated by Bcl2l1 is crucial for various biological processes such as bone homeostasis, and it is also involved in pathways related to cell survival, mitophagy, and is associated with multiple diseases [1,3]. Genetic models, like knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions.

In osteoblast-specific Bcl2l1-deficient (Bcl2l1fl/flCre) mice, trabecular bone volume and number were lower. The deletion led to increased osteoclast parameters, osteoblast apoptosis, and Tnfsf11 expression. This indicates that Bcl2l1 may inhibit bone resorption by preventing osteoblast apoptosis [1]. In breast cancer cell lines and syngeneic models, inhibition of Bcl2l1 combined with radiotherapy dramatically impeded tumor growth, suggesting a potential anticancer strategy [2].

In conclusion, Bcl2l1 is essential for maintaining cell survival by regulating apoptosis. Its deficiency in osteoblasts impacts bone homeostasis, and its inhibition shows promise in cancer treatment when combined with radiotherapy. The study of Bcl2l1 using KO/CKO mouse models provides insights into bone-related diseases and cancer, helping to understand disease mechanisms and develop new treatment strategies.