KDM1A (lysine demethylase 1A) is a histone demethylase that functions as a key epigenetic regulator of gene transcription. The enzyme specifically demethylates histone H3 lysine 4 (H3K4me1/2) through an oxidation reaction that generates formaldehyde, leading to transcriptional repression 1. KDM1A also exhibits H3K9me2 demethylase activity through cooperation with supervillin protein, essential for neuronal differentiation [UniProt]. The protein acts as a transcriptional corepressor, with RNAi inhibition causing increased H3K4 methylation and target gene derepression 1. KDM1A plays critical roles in cancer biology, promoting tumor progression and maintaining cancer stem cell properties through activation of the Wnt/β-catenin pathway by suppressing pathway antagonists APC2 and DKK1 2. In skin homeostasis, KDM1A collaborates with ZNF750 to silence pattern recognition receptors in differentiated keratinocytes, preventing excessive inflammation 3. The enzyme is implicated in breast cancer metastasis through epigenomic remodeling that facilitates MAF/estrogen-driven gene expression programs 4. Clinically, KDM1A represents a therapeutic target, with selective inhibitors like ORY-1001 showing promise in acute leukemia treatment 5. Germline KDM1A mutations are associated with primary bilateral macronodular adrenal hyperplasia 6.