EVX2 (even-skipped homeobox 2) is a transcription factor gene located at the 5' end of the HOXD cluster on chromosome 2 1. EVX2 encodes a homeodomain-containing protein that represents the human homolog of the Drosophila even-skipped segmentation gene 1. The protein functions as a sequence-specific DNA-binding transcription factor involved in developmental regulation, particularly in limb and digit formation 2. EVX2 is transcriptionally active and properly processed in human cells and tissues 1. Mechanistically, EVX2 participates in chr2-mediated regulatory processes, with a functionally conserved boundary element between EVX2 and HOXD13 that helps separate distinct regulatory domains 3. This boundary element requires GAGA factor binding and contributes to the spatial organization of gene expression within the HOXD cluster 3. Disease relevance includes its role in limb malformations, as microdeletions removing EVX2 along with HOXD9-HOXD13 cause synpolydactyly, a dominantly inherited digital anomaly 2. Additionally, EVX2 amplification has been observed in ovarian mature cystic teratomas and may contribute to abnormal chondrogenesis and osteogenesis in these tumors 4. EVX2 promoter hypermethylation has also been identified as a potential biomarker in lung cancer 5.