Safb2, also known as scaffold attachment factor-B2, is a multifunctional protein. It has been implicated in multiple cellular processes such as chromatin organization, transcriptional regulation, RNA splicing, and stress response [3,4]. It functions as an estrogen receptor corepressor and is thought to have potential tumor-suppressing properties [3,4,5]. It also plays a role in miRNA processing, enabling the processing of suboptimal stem-loop structures in clustered primary miRNA transcripts [2].

SAFB2-null mice were generated to assess its in vivo role [6]. Unlike SAFB1-knockout mice which display high lethality, growth retardation, and infertility in males, SAFB2-null offspring were born at expected ratios and showed no obvious growth or fertility defects. However, SAFB2-null mice had significantly increased testis weight associated with an increased number of Sertoli cells, suggesting a role for SAFB2 in Sertoli cell differentiation and activity [6]. In breast cancer, SAFB2 is downregulated, and its overexpression suppresses cancer cell proliferation, migration, and invasion while promoting apoptosis. It interacts with NFAT5 mRNA, decreasing its stability, and inhibits the Wnt/β-catenin signaling pathway [1].

In conclusion, SAFB2 has diverse functions in the cell, including roles in miRNA processing, transcriptional regulation, and as a potential tumor suppressor. The generation of SAFB2-null mice has revealed its non-redundant functions, especially in Sertoli cell-related processes. In breast cancer, its dysregulation and role in signaling pathways suggest it could be a promising therapeutic target.