TOM1L2 (target of myb1 like 2 membrane trafficking protein) is a versatile membrane trafficking protein with critical roles in endosomal sorting and cellular homeostasis. The protein functions as a key component of the ESCRT (endosomal sorting complexes required for transport) machinery, directly binding to lysine 63-linked ubiquitin chains to facilitate the retrieval of ubiquitinated proteins from cellular compartments 1. In cilia, TOM1L2 works with the BBSome complex to recognize and remove ubiquitinated G protein-coupled receptors, enabling proper signal transduction 1. The protein also plays important roles in xenophagy, where it recruits ESCRT components through the Rab41 pathway to repair membrane damage caused by bacterial toxins 2. Additionally, TOM1L2 facilitates mitochondrial repair by mediating membrane fusion between therapeutic mitochondrial extracellular vesicles and damaged neuronal mitochondria 3. Loss of TOM1L2 function has significant physiological consequences, as hypomorphic mice exhibit increased susceptibility to infections and tumors, along with abnormal immune responses including splenomegaly and impaired humoral immunity 4. The protein has emerged as a potential drug target for neurodegenerative diseases, with studies identifying it as causally associated with Alzheimer's disease risk 56 and various ocular diseases 7, highlighting its clinical significance in maintaining cellular and tissue homeostasis.