TOM1L1 (Target of Myb1 Like 1 Membrane Trafficking Protein) is a multifunctional adapter protein that plays crucial roles in membrane trafficking and cellular signaling. The protein contains VHS and GAT domains characteristic of the Tom1 protein family and functions as an intermediary between signaling and degradative pathways 1. TOM1L1 interacts with key components of the multivesicular body (MVB) sorting machinery, including Hrs through its VHS domain and TSG101 via a PTAP motif, suggesting involvement in sorting ubiquitinated proteins into MVBs 1. The protein is recruited to clathrin-coated pits where it regulates EGFR signaling and Akt2 phosphorylation in collaboration with Fyn kinase 2. In cancer contexts, TOM1L1 demonstrates significant clinical relevance. It is co-amplified with ERBB2 in breast cancer and promotes tumor cell invasion by facilitating MT1-MMP delivery to invadopodia through ERBB2-induced phosphorylation at Ser321 3. Additionally, TOM1L1 expression levels correlate with chemotherapy response in colorectal cancer, where low expression predicts better sensitivity to neoadjuvant treatment 4. The protein also shows prognostic significance in gliomas, where it modulates posttranslational modification pathways and serves as a potential therapeutic target 5.