IST1 is an ESCRT-III-associated protein with essential roles in membrane dynamics and cellular homeostasis. Functionally, IST1 acts as a key regulator of cytokinesis, nuclear envelope reassembly, and endosomal trafficking 1. Mechanistically, IST1 recruits VPS4A/B to the midbody during cytokinesis to facilitate efficient abscission 1, and recruits SPAST to remodeling nuclear envelopes during mitotic spindle disassembly 2. IST1 also mediates endosomal tubulation through SPAST-dependent mechanisms 3. Additionally, IST1 forms friction-driven membrane scission scaffolds with CHMP1B that constrict membrane tubes independently of VPS4 4, and participates in Rab11a-dependent exosome biogenesis 5. Disease relevance includes cancer progression, where IST1 enhances ESCRT-III complex assembly with CHMP4B to maintain autophagic flux in hepatocellular carcinoma 6, and neurotoxic responses, where IST1 overexpression alleviates acrylamide-induced apoptosis through autophagy restoration 7. Clinically, IST1 upregulation is associated with improved cardiac outcomes in heart failure patients treated with SGLT2 inhibitors, suggesting roles in cellular quality control and ATP production 8. IST1 also participates in lysosomal damage sensing and lysophagy initiation 9.