TSG101 is a multidomain protein and core component of the ESCRT-I complex that regulates vesicular trafficking and cellular homeostasis 1. Its primary function involves binding ubiquitinated cargo proteins and sorting them into multivesicular bodies for endosomal degradation 2. TSG101 is essential for cytokinesis completion and mediates ESCRT-0 to ESCRT-I complex transitions 1. The protein also regulates exosomal release of cargo molecules including CD63 and syndecan, with evidence supporting roles in extracellular microvesicle biogenesis 3. Beyond endosomal sorting, TSG101 plays critical roles in innate immunity by facilitating STING degradation through ESCRT-dependent microautophagy, preventing hyperactivation of interferon responses 4. TSG101 is also recruited to endolysosomal damage sites where it participates in membrane repair mechanisms 5. Clinically significant is TSG101's hijacking by enveloped viruses: the P(T/S)AP-binding pocket in TSG101's N-terminal domain recruits viral late-budding motifs, enabling HIV-1 and coronavirus budding and replication 67. TSG101 depletion impairs viral particle release, making it an attractive anti-viral therapeutic target 8. Additionally, TSG101 functions as a negative growth regulator implicated in tumorigenesis 1, suggesting potential relevance in cancer biology.