Anti-CD148 antibodies and antigen-binding regions thereof, as well as pharmaceutical compositions comprising such antibodies and antigen-binding regions, are described. Also described are methods of using such antibodies and antigen-binding regions to bind CD148 epitopes and activate CD148 function, such as inhibition of angiogenesis. Epitopes that can be used to activate CD148 function and anti-angiogenesis activity are also described, as well as methods of identifying compounds that can bind them.