BBC3 (BCL2 binding component 3), also known as PUMA (p53 upregulated modulator of apoptosis), is a proapoptotic BH3-only protein that serves as an essential mediator of both p53-dependent and p53-independent apoptosis 1. The protein functions by promoting partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53, thereby releasing bound p53 to induce apoptosis. BBC3 operates through the BAX/BBC3/AKT signaling pathway and upregulates the BBC3-CASP9-CASP3 apoptotic cascade 2. The gene plays crucial roles in various pathological conditions: it contributes to trophoblast cell apoptosis and recurrent miscarriage when its chaperone-mediated autophagy degradation is impaired 3, participates in cold preservation-induced pancreatic islet injury through modulation of oxidative stress 4, and promotes pulmonary fibrosis by inducing autophagy in macrophages during silicosis 5. Clinically, BBC3 serves as a potential biomarker for breast cancer diagnosis and prognosis 1 and is dysregulated in gastric cancer where its mRNA degradation promotes cancer progression 6. BBC3 expression is also altered in idiopathic pulmonary fibrosis, suggesting its involvement in ferroptosis-related mechanisms 7.