The protein encoded by the Tumor Susceptibility Gene 101 (Tsg101) has a variety of important functions including the regulation of cellular proliferation, endosomal sorting of growth factor receptors, and viral budding. Tsg101 was originally identified in a screen for potential tumor suppressors, but this gene may actually be an oncogene since it has been shown to be overexpressed in a subset of breast and ovarian cancers. Deficiency in Tsg101 in various cell lines causes severe growth inhibition and cell death due to the inactivation of cyclin-dependent kinase 2, causing a growth arrest at the G1/S checkpoint. Other recent studies suggest that Tsg101 also plays a central role in the regulation of endosomal sorting, allowing for the recruitment of ESCRT-1, an endosomal sorting complex, to the endosome. Interestingly, because of its importance in the regulation of endosomal sorting, Tsg101 has been shown to be important in the regulation of viral budding. Researchers at The University of Nebraska Medical Center have developed a Tsg101 conditional knockout mouse. The mating of a conditional Tsg101 mouse with an MMTV-Cre strain has resulted in the excision of the first coding exon of the Tsg101 alleles that contains the transcriptional start codon thus creating a Tsg101 null mutation. Due to the variety of cellular functions controlled by Tsg101, this conditional knockout model will be a valuable tool for further understanding the role of Tsg101.