Special AT-rich sequence-binding protein 2 (SATB2) also known as DNA-binding protein SATB2 is a protein that in humans is encoded by the SATB2 gene. SATB2 specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin remodeling.  SATB2 has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome.

SATB2 has been identified as a tissue-specific protein when screening protein expression patterns in human and cancerous tissues, with expression restricted to the lower gastrointestinal tract. SATB2 in combination with CK20 and Cadherin 17 could identify almost all colorectal carcinomas, including poorly differentiated colorectal carcinomas. Upper gastrointestinal (GI) carcinomas and pancreatic ductal carcinomas are usually negative for SATB2, and ovarian carcinomas, lung adenocarcinomas, and adenocarcinomas from other origin are rarely positive for SATB2. Therefore, SATB2 is a good marker for identifying a carcinoma of colorectal origin when working on a tumor of unknown primary. Another potential utility of SATB2 is to identify neuroendocrine neoplasms/carcinomas of the colon and rectum because SATB2 is usually negative in other neuroendocrine neoplasms of the GI tract, pancreas, and lung. STAB2 has been also shown to be a sensitive marker of osteoblastic differentiation in benign and malignant mesenchymal tumors.