Target of Myb1 (TOM1) (TOM1)

Target of Myb1 (TOM1) is a critical component of the endosomal trafficking machinery, primarily functioning in the sorting of ubiquitinated proteins for lysosomal degradation (UniProt O60784). It contains a VHS domain that binds ubiquitin and a GAT domain that interacts with the adapter protein TOLLIP, together regulating the internalization and signaling of receptors such as Toll-like receptors (TLRs) and interleukin-1 receptors (PubMed: 33024319). In neurodegenerative contexts, specifically Alzheimer's disease, TOM1 is essential for the endosomal-lysosomal clearance of amyloid-beta; studies have shown that TOM1 expression is significantly reduced in the hippocampi of Alzheimer's patients, correlating with increased amyloid pathology (PubMed: 31570702). Conversely, genetic deficiency of TOM1 in humans leads to a syndrome of immunodeficiency and autoimmunity due to the failure to properly downregulate inflammatory signaling (PubMed: 33024319). While there are currently no FDA-approved drugs targeting TOM1 mRNA, it is an emerging target for RNA-based therapeutic modalities such as antisense oligonucleotides (ASOs) or mRNA replacement therapies aimed at restoring its function in neurodegeneration or modulating it in inflammatory disorders. Potential safety concerns for targeting TOM1 mRNA include the risk of off-target effects common to RNA therapeutics and the possibility of inducing systemic immune imbalances given its central role in innate immune regulation.

Other names

Target of Myb protein 1TOM1

Antisense inhibition; RNA interference; mRNA replacement