CUL4B is a scaffold protein that forms the core of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL4B), which mediate ubiquitination and proteasomal degradation of target proteins 1. The functional specificity depends on variable substrate recognition subunits, with CUL4B positioning substrates and ubiquitin-conjugating enzymes for catalysis 1. CUL4B plays critical roles in DNA damage repair by ubiquitinating histones H2A, H3, and H4 in response to radiation-induced damage 1. In cell cycle regulation, CUL4B controls G1-to-S phase transition through ubiquitination of cyclins D and E 1. CUL4B is essential for neuronal development and synaptic function, with deficiency causing synaptic abnormalities, impaired spatial learning and memory 1. The protein regulates cortical neurogenesis by preventing premature cell cycle exit through PP2A-dependent inhibition of AKT and ERK signaling pathways 2. Loss-of-function mutations in CUL4B cause X-linked intellectual disability (Cabezas type), characterized by developmental delays and learning difficulties 3. CUL4B also protects against acute kidney injury by restraining p53/PAI-1 signaling 4 and modulates immune responses in various contexts 5.