KDM1B (lysine demethylase 1B) is an FAD-dependent histone demethylase that catalyzes oxidative removal of mono- and di-methylation marks at histone H3 lysine 4 (H3K4me1/2), a modification associated with transcriptional activation 1. Unlike the closely related LSD1, KDM1B localizes predominantly to gene bodies rather than promoters, regulating transcription elongation through intragenic H3K4 demethylation and forming functional complexes with histone methyltransferases and transcription factors 1. KDM1B also plays essential roles in oogenesis and genomic imprinting, with upregulation observed during oocyte development 2. Clinically, KDM1B dysregulation drives multiple malignancies. Type I interferons promote cancer stem cell formation via KDM1B activation, enhancing chemoresistance and immune escape 3. In prostate cancer, elevated KDM1B correlates with enzalutamide resistance through the miR-215-AR-AGR2 axis 4, while diffuse large B cell lymphoma shows inverse miR-215/KDM1B expression correlating with poor prognosis 5. Beyond cancer, KDM1B suppresses white adipose tissue browning via BAP1-mediated deubiquitination, contributing to obesity 6, and drives osteoarthritis progression by epigenetically suppressing SOX9 7. KDM1B overexpression enhances somatic cell reprogramming toward pluripotency 8. These findings establish KDM1B as a pivotal epigenetic regulator in disease pathogenesis, supporting therapeutic targeting strategies.