Bcl2l1, also known as Bcl-XL, belongs to the Bcl-2 family. It is a major anti-apoptotic protein, and the apoptosis regulated by it is crucial for maintaining bone homeostasis, cell survival in various tissues, and is involved in multiple biological pathways such as mitophagy [2,4].

In osteoblast-specific Bcl2l1-deficient (Bcl2l1fl/flCre) mice, trabecular bone volume and number decreased due to enhanced osteoclastogenesis likely through osteoblast apoptosis. The deletion of Bcl2l1 in osteoblasts induced Tnfsf11 expression, increased apoptosis and ATP levels in the medium, suggesting that Bcl2l1 inhibits bone resorption by preventing osteoblast apoptosis [2].

In addition, in cancer research, inhibition of Bcl2l1 protein activity decreased γ-globin (HBG) gene expression in a dose-dependent manner in HbF-expressing HUDEP-1 cells, while overexpression increased HBG expression. Also, Bcl2l1 inhibition combined with radiotherapy dramatically impeded tumor growth in several breast cancer cell lines and syngeneic models, indicating its importance in tumor cell survival after radiation [1,3].

In conclusion, Bcl2l1 is essential for maintaining cell survival and preventing apoptosis in various cell types. Its function is crucial in bone homeostasis as demonstrated by the Bcl2l1-deficient mouse model, and it also plays significant roles in diseases such as cancer, where its manipulation shows potential in therapeutic strategies.