The NF-κB-inducing kinase: a central regulator of immunity and autoimmune diseases

The NF-κB-inducing kinase (NIK) plays a central role in mediating activation of the non-canonical NF-κB pathway. Recent studies have identified additional signaling functions of NIK, including regulation of metabolism and mitochondrial function. NIK serves as a key signaling mediator of a subset of TNF receptor (TNFR) superfamily members and is involved in diverse functions of the immune system, including lymphoid organ development, B cell survival and maturation, and T cell effector function. Dysregulated NIK signaling is associated with immunodeficiencies and autoimmune diseases, as demonstrated in both animal model and human patient studies. This review will focus on the physiological and pathological functions of NIK in the immune system and highlight the therapeutic implications.