NLK (nemo-like kinase) is a serine/threonine-protein kinase that regulates cell fate determination through phosphorylation of multiple transcription factors 123. As an atypical MAPK enzyme, NLK functions as a negative regulator of canonical Wnt/β-catenin signaling by phosphorylating TCF7L2/TCF4 and LEF1, promoting their dissociation from DNA and subsequent proteolysis, thereby inhibiting transcription of Wnt target genes 14. Conversely, NLK acts as a positive effector of non-canonical Wnt/WNT5A signaling, operating downstream of MAP3K7/TAK1 and HIPK2 35. Additionally, NLK negatively regulates Notch signaling by phosphorylating NOTCH1 to prevent formation of transcriptionally active complexes 6, and inhibits MYB family transcription factors through direct phosphorylation 7. NLK also coordinates with ATF5 to modulate C/EBP activity upon IL1B stimulation 8 and acts as an mTORC1 inhibitor during osmotic stress by phosphorylating RPTOR 9. These diverse regulatory functions position NLK as a critical mediator of developmental signaling and cellular stress responses. Disease relevance and specific clinical applications are not addressed in available abstracts.