Trophoblast cell surface antigen 2 (Trop2) is a widely expressed glycoprotein 
and an epithelial cell adhesion molecule (EpCAM) family member. Although 
initially identified as a transmembrane protein, other subcellular localizations 
and processed forms were described. Its congenital mutations cause a gelatinous 
drop-like corneal dystrophy, a disease characterized by loss of barrier function 
in corneal epithelial cells. Trop2 is considered a stem cell marker and its 
expression associates with regenerative capacity in various tissues. Trop2 
overexpression was described in tumors of different origins; however, functional 
studies revealed both oncogenic and tumor suppressor roles. Nevertheless, 
therapeutic potential of Trop2 was recognized and clinical studies with 
drug-antibody conjugates have been initiated in various cancer types. One of 
these agents, sacituzumab govitecan, has been recently granted an accelerated 
approval for therapy of metastatic triple-negative breast cancer. In this 
article, we review the current knowledge about the yet controversial function of 
Trop2 in homeostasis and pathology.