TSPAN17 is a member of the TspanC8 subgroup of tetraspanins that functions as a critical regulator of ADAM10, a transmembrane metalloprotease with over 100 substrates 1. TSPAN17 directly interacts with ADAM10 to regulate its exit from the endoplasmic reticulum, enzymatic maturation, trafficking to the cell surface, and substrate specificity 2. Different TspanC8/ADAM10 complexes, including those containing TSPAN17, function as distinct "molecular scissors" with different substrate preferences 1. Specifically, TSPAN17 and Tspan5 form complexes with ADAM10 that regulate VE-cadherin expression in endothelial cells and promote T lymphocyte transmigration across the endothelial barrier 3. TSPAN17 also influences ADAM10 endocytosis and cell surface stability, though less dramatically than some other TspanC8 members 4. Clinically, TSPAN17 expression is associated with disease outcomes in multiple cancers. In glioblastoma multiforme, high TSPAN17 expression correlates with poor prognosis and larger tumor sizes, and TSPAN17 suppression by miR-378a-3p reduces cellular proliferation, migration, and invasion 5. Additionally, upregulated TSPAN17 expression associates with FOLFOX chemotherapy responsiveness in metastatic colorectal cancer 6, suggesting potential therapeutic targeting of TSPAN17-containing complexes.