The signal transducer and activator of transcription 5B (STAT5B) gene is a member of the STAT family of transcription factors, which has as its other member, STAT5A. Both these genes have 90% sequence identity. The STAT5B protein, in response to cytokines and growth factors, such as interleukin 2, interleukin 4, and colony stimulating factor 1 and other growth hormones, gets phosphorylated by receptor associated kinases on proteins such as growth hormone receptors. Following this phosphorylation, the STAT proteins form homo-or hetero-dimers and translocate to the nucleus, where they act as transcription activators of several genes, including many involved in T cell receptor signaling, apoptosis, adult mammary gland development, sexual dimorphism of liver gene expression, and others.

Mutations in the STAT5B gene have been shown to cause a form of growth hormone insensitivity due to postreceptor defect, characterized by severe growth failure, in the presence of normal-to-elevated concentrations of circulating growth hormone and resistance to exogenous growth hormone therapy. In addition, the STAT5B gene was found to fuse to retinoic acid receptor-alpha (RARA) gene in a small subset of acute promyelocytic leukemias.

The STAT5B gene is a 36 kb stretch of DNA on chromosome 17. It consists of 19 exons that, together, transcribe an mRNA of about 5kb. The STAT5B protein is made of 787 amino acids and weighs about 90 kDa. The protein, as explained above, carries out a dual function, that of signal transduction as well as of a transcription activator.