MYCL is a proto-oncogene encoding a bHLH transcription factor that functions as a key regulator of cellular proliferation and transcriptional reprogramming. As a member of the MYC family, MYCL modulates approximately 15% of the global transcriptome, orchestrating diverse physiological processes including cell proliferation, differentiation, survival, and apoptosis 1. MYCL localizes to the nucleus where it binds RNA polymerase II cis-regulatory regions to regulate transcription [GO annotations]. In cancer, MYCL drives tumorigenesis primarily through gene fusion and amplification mechanisms. RLF-MYCL fusion—occurring in up to 7% of ASCL1-expressing small cell lung cancer (SCLC)—accelerates transformation, increases proliferation, and promotes metastatic dissemination 2. Extrachromosomal circular DNA-mediated MYCL amplification (ecMYC+) shapes an immunosuppressive tumor microenvironment, correlating with reduced T-cell infiltration and therapy resistance 3. MYCL overexpression confers resistance to therapeutic intervention, with MAX acting as a context-dependent tumor suppressor that restrains MYCL-driven tumorigenesis 4. Clinically, MYCL amplification and overexpression are associated with poor prognosis in lung cancer 5. However, MYCL exhibits therapeutic potential beyond oncology: transient MYCL expression expands functional pancreatic β-cells and reverses hyperglycemia in diabetic mice 6, while MYCL co-expression with MYOD1 efficiently converts human fibroblasts into myogenic cells for regenerative therapy 7. MYCL also enhances induced pluripotent stem cell generation more efficiently than c-MYC 8.