FAM19A (TAFA): An Emerging Family of Neurokines with Diverse Functions in the Central and Peripheral Nervous System.

Cytokines and chemokines have diverse and pleiotropic functions in peripheral tissues and in the brain. Recent studies uncovered a novel family of neuron-derived secretory proteins, or neurokines, distantly related to chemokines. The FAM19A family comprises five ∼12-15 kDa secretory proteins (FAM19A1-5), also known as TAFA1-5, that are predominantly detected in the central and peripheral nervous system. FAM19A expression in the central nervous system is dynamically regulated during development and in the postnatal brain. As secreted ligands, FAM19A proteins appear to bind to different classes of cell surface receptors (e.g., GPCRs and neurexins). Functional studies using gain- and loss-of-function mouse models established nonredundant roles for each FAM19A family member in regulating diverse physiological processes ranging from locomotor activity and food intake to learning and memory, anxiety- and depressive-like behaviors, social communication, repetitive behaviors, and somatosensory functions. This review summarizes major advances as well as the limitations and knowledge gaps in understanding the regulation and diverse biological functions of this conserved family of neurokines.