SULT2B1 (sulfotransferase family 2B member 1) encodes two isoforms, SULT2B1a and SULT2B1b, through alternative transcription initiation and splicing from a single gene on chromosome 19 1. Both isoforms are phase II metabolizing enzymes that catalyze sulfation of 3β-hydroxysteroids, with SULT2B1a preferentially sulfonating pregnenolone and SULT2B1b showing high cholesterol sulfation activity 2 3. The enzymes contain unique proline/serine-rich carboxy-terminal sequences and show nuclear localization in selected tissues related to serine phosphorylation 3. SULT2B1 is expressed in human placenta, prostate, trachea, small intestine, and lung 1. The gene exhibits significant disease relevance, with mutations causing autosomal recessive congenital ichthyosis type 14 4. In cancer biology, SULT2B1 promotes tumor progression through multiple mechanisms: it facilitates colon cancer metastasis by interacting with SCD1 to enhance lipid metabolism 5, promotes T-cell exhaustion in hepatocellular carcinoma through cholesterol sulfate synthesis 6, and acts as an oncogene in colorectal cancer by modulating AKT/PKM2-mediated glycolysis and proliferation 7. These findings establish SULT2B1 as both a critical regulator of steroid homeostasis and a potential therapeutic target in cancer treatment 8.