BAMBI, short for bone morphogenetic protein and activin membrane-bound inhibitor, is a transmembrane pseudoreceptor structurally related to transforming growth factor (TGF)-β type 1 receptors. Lacking a kinase domain, it functions as a TGF-β1R antagonist, regulating key processes like cell differentiation, proliferation, glucose and lipid metabolism, and inflammatory responses [3,5]. It is involved in multiple signaling pathways, such as TGF-β/SMAD, WNT/β-catenin, and is crucial in various biological and pathological contexts [1].

In hepatocellular carcinoma (HCC), PPARGC1A represses BAMBI by inhibiting WNT/β-catenin signaling. BAMBI then mediates PPARGC1A's function and regulates ACSL5 through TGF-β/SMAD signaling, with the PPARGC1A/BAMBI/ACSL5 axis being hypoxia-responsive and affecting HCC progression and lenvatinib resistance [1]. In immune cells, ionizing radiation reduces BAMBI expression in myeloid-derived suppressor cells (MDSCs) via YTHDF2-mediated m6A-dependent degradation, and BAMBI suppresses MDSCs' functions by inhibiting TGF-β signaling. AAV-Bambi delivery to the tumor microenvironment enhances radiotherapy effects [2]. In liver fibrosis, hepatic BAMBI is downregulated in rodent injury models and fibrotic livers of patients, and its overexpression can protect against liver fibrosis [3]. In sheep luteinized follicular granulosa cells, BAMBI regulates cell proliferation and steroid hormone synthesis [4]. In skeletal muscle, BAMBI protein shuttles between the cytosol and membrane during muscle growth and regeneration [6].

In conclusion, BAMBI plays diverse and significant roles in multiple biological processes and diseases. Studies using various models, though not specifically KO/CKO mouse models in the provided references, have revealed its importance in areas like cancer, fibrosis, ovarian function, and muscle development. Understanding BAMBI could potentially offer new insights for disease treatment and prevention related to these biological functions [1,2,3,4,6].