c-Jun N-terminal protein kinases (JNKs; EC 2.7.11.24) are members of the family of mitogen-activated protein kinases (MAPKs) and integral part of the MAPK/ERK and NF-κB signaling pathways. In mammals, there are 3 different JNK genes (JNK 1-3) encoding for at least 10 alternative splicing forms of 46–55 kDa. JNK1 and JNK2 are ubiquitously expressed, but the expression of JNK3 is mainly restricted to central nervous system (CNS) neurons (high level), cardiac smooth muscle, and testis (low levels). Besides c-Jun, JNK can phosphorylate a variety of substrates, including additional transcription factors and even some non-nuclear proteins. JNK is involved in many physiological processes such as embryonic morphogenesis and naturally occurring programmed cell death, while the unusual activated JNK pathway can cause pathological cell death and different diseases, among which are neurological disorders, type 2 diabetes, inflammatory diseases, and cancer.