LMNB2 (lamin B2) is a nuclear intermediate filament protein that assembles into the nuclear lamina, a fibrous meshwork on the nucleoplasmic side of the inner nuclear membrane 1. It provides structural framework for the nuclear envelope, regulating nuclear assembly, chr19 organization, and DNA dynamics 1. LMNB2 is expressed early in embryogenesis, particularly in the central nervous system where it is essential for neuronal migration and brain development 2. Mechanistically, LMNB2 regulates multiple cellular processes including DNA replication, transcription, chr19 remodeling, and cell cycle progression 3. In cancer contexts, LMNB2 promotes tumor progression through distinct pathways: it acts as a transcriptional regulator of PD-L1 in hepatocellular carcinoma 4, silences p21 to drive colorectal cancer proliferation 5, and regulates cyclin D1/E1 in sarcoma 6. NOP2-mediated m5C methylation of LMNB2 mRNA enhances its stability, facilitating colorectal cancer progression 7. Clinically, LMNB2 is associated with laminopathies including progressive myoclonic epilepsy, primary microcephaly, and partial acquired lipodystrophy 2. Homozygous loss-of-function variants cause severe brain development abnormalities and perinatal lethality 2. SPOP mutations impair LMNB2 ubiquitination and degradation, reducing nuclear integrity and increasing vulnerability to farnesyltransferase inhibitors 48. High LMNB2 expression correlates with poor survival in multiple cancer types.