The present disclosure provides antibodies that specifically bind to human FAM19A5 and compositions comprising such antibodies. In some embodiments, antibodies are de-immunized to reduce immunogenicity in a human subject. In certain embodiments, antibodies have undergone affinity maturation. In some embodiments, the anti-FAM19A5 antibodies can modulate FAM19A5 activity, e.g, inhibit, suppress, reduce, or reverse the onset of reactive gliosis and/or excessive proliferation of reactive astrocytes, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as central nervous system damage, a degenerative brain disorder, a neuropathic pain, or a cancer, by administering an antibody that specifically binds to human FAM19A5.