SALL3 (spalt like transcription factor 3) is a zinc finger transcription factor located on chromosome 18 that functions as a developmental regulator and tumor suppressor 1. The protein acts as a DNA-binding transcription factor with RNA polymerase II-specific activity, operating through direct interaction with epigenetic regulators. Mechanistically, SALL3 inhibits DNA methyltransferase 3A (DNMT3A) by binding to its PWWP domain through its double zinc finger motif, thereby suppressing aberrant CpG island methylation 2. Additionally, SALL3 modulates DNA methyltransferase activity and influences gene body methylation patterns, serving as a critical regulator of cell lineage differentiation in pluripotent stem cells 3. SALL3 expression correlates positively with ectodermal differentiation while inversely regulating mesoderm/endoderm differentiation capacity 3. In neural development, SALL3 promotes dopaminergic neuron differentiation by regulating tyrosine hydroxylase expression 4. Clinically, SALL3 functions as a tumor suppressor; its aberrant promoter hypermethylation and subsequent downregulation occur in hepatocellular carcinoma 5 and cervical cancer, particularly in HPV-positive cases 6. Loss of SALL3 impairs neuroectodermal differentiation and alters pluripotency states 7, while SALL3 haploinsufficiency may contribute to 18q deletion syndrome phenotypes 1.