Becn2, also known as beclin 2, is a mammalian-specific member of the macroautophagy/autophagy family. It plays a critical role in multiple biological processes, mainly through its involvement in non-canonical autophagy pathways. It has been linked to the regulation of inflammation, tumor development, and drug-related behaviors, and its study using genetic models has provided insights into these functions [1,2,3].

Loss-of-function experiments in mice have revealed key roles of Becn2. Mice lacking Becn2 show enhanced inflammasome activities, promoting alum-induced peritonitis, which can be rescued by Casp1 ablation, indicating its role in negatively regulating inflammasome activation and controlling inflammation [1]. Becn2-deficient mice also develop splenomegaly, lymphadenopathy, elevated pro-inflammatory cytokine production, and spontaneous lymphoma development. Mechanistically, Becn2 mediates degradation of MAP3K7/TAK1 and MAP3K3/MEKK3 through an ATG9A-and ULK1-dependent but ATG16L1-BECN1-MAP1LC3B/LC3B-independent autophagy pathway [2]. Moreover, Becn2 deletion protects mice from cocaine-stimulated locomotion, reward behaviors, and cocaine-induced dopamine accumulation by increasing presynaptic dopamine receptor 2 autoreceptors in dopamine neurons [3].

In conclusion, Becn2 is essential in regulating innate immune signaling, tumor development, and drug-related behaviors through non-canonical autophagy. Studies using Becn2 KO/CKO mouse models have provided crucial insights into its functions, highlighting its potential as a therapeutic target for inflammatory diseases, cancer, and drug-related disorders [1,2,3].