The present invention relates to antibodies and related molecules that specifically bind to TL5. Such antibodies have uses, for example, in the prevention and treatment of cancer as well as immune system diseases and disorders including autoimmune disease, rheumatoid arthritis, graft rejection, graft vs. host disease, and lymphadenopathy. The invention also relates to nucleic acid molecules encoding anti-TL5 antibodies, vectors and host cells containing these nucleic acids, and methods for producing the same. The present invention relates to methods and compositions for preventing, detecting, diagnosing, treating or ameliorating a disease or disorder, especially cancer as well as immune system diseases and disorders including autoimmune disease, rheumatoid arthritis, graft rejection, graft vs. host disease, and lymphadenopathy, comprising administering to an animal, preferably a human, an effective amount of one or more antibodies or fragments or variants thereof, or related molecules, that specifically bind to TL5.