RBCK1 (RANBP2-type and C3HC4-type zinc finger containing 1) is a critical E3 ubiquitin ligase that functions as a component of the Linear Ubiquitin Chain Assembly Complex (LUBAC) 1. The protein primarily mediates linear ('Met-1'-linked) polyubiquitin chain conjugation to substrates, playing essential roles in NF-κB activation and inflammation regulation. RBCK1 promotes the degradation of specific substrates including oxidized IREB2, TAB2, and IRF3 through the proteasome pathway 1. As part of LUBAC, RBCK1 conjugates linear polyubiquitin chains to key signaling proteins such as IKBKG and RIPK1, thereby activating canonical NF-κB and JNK signaling pathways. The complex also contributes to innate immunity by forming ubiquitin coats on cytosolic bacteria to promote xenophagy 1. Additionally, RBCK1 regulates autophagy initiation and maturation by mediating linear ubiquitination and stabilization of ATG13 1. Clinically, mutations in RBCK1 cause Polyglucosan Body Myopathy 1 (PGBM1), characterized by muscle weakness, cardiomyopathy, and polyglucosan accumulation in tissues 2 3 4. In cancer, RBCK1 exhibits oncogenic properties, particularly in clear cell renal cell carcinoma where it contributes to sunitinib resistance through the ANKRD35-MITD1-ANXA1 axis 5 6.