VPS28 is a key component of the ESCRT-I complex that regulates vesicular trafficking and multivesicular body sorting pathways 1. The protein directly interacts with TSG101 to form a multiprotein complex involved in endosomal sorting, with both proteins translocating to endosomal surfaces when endosomal vacuolization occurs 1. VPS28 functions in viral budding processes, where it interacts with viral matrix proteins to facilitate assembly and egress of β-coronaviruses 2 and influenza viruses 3. In coronavirus infection, VPS28 specifically interacts with viral M protein and is required for late-stage virion assembly 2. The protein also plays a role in drug resistance mechanisms in glioblastoma, where it promotes exosome secretion and decreases intracellular temozolomide concentration, contributing to chemotherapy resistance 4. ESCRT-I deficiency, including VPS28 depletion, triggers metabolic reprogramming through activation of NFκB and JNK signaling pathways, leading to Warburg effect-like changes with increased glycolysis and altered lipid metabolism 5. Additionally, LRSAM1 acts as a regulator of VPS28 expression, and deregulation of this pathway is associated with Charcot-Marie-Tooth disease 6.