CKMT1B (creatine kinase, mitochondrial 1B) is a mitochondrial energy metabolism enzyme that catalyzes reversible phosphoryl transfer from ATP to creatine, supporting cellular energy homeostasis 1. While CKMT1B is highly expressed in mitochondria-dependent cells, it appears functionally distinct from CKB in regulating mitochondrial ATP production through the permeability transition pore pathway 1. In colorectal cancer, CKMT1B functions as a tumor suppressor gene, with reduced expression enhancing cancer cell proliferation, migration, and invasion while suppressing apoptosis through the AKT/mTOR/STAT3 pathway 2. Similarly, low CKMT1B expression predicts worse prognosis in lower-grade glioma and associates with reduced immune infiltration 3. Genetically, loss-of-function variants in CKMT1B correlate with reduced human lifespan primarily through cancer-related pathways 4. Beyond oncology, CKMT1B plays essential roles in male fertility, with its Drosophila homolog AK-3 required for axonemal microtubule assembly during spermiogenesis, a function conserved in humans 5. CKMT1B expression also shows sex-dimorphic associations with body mass index and metabolic function 6. In CNS infections, downregulated CKMT1B in cerebrospinal fluid associates with varicella zoster meningitis pathogenesis 7. Collectively, CKMT1B represents a multifunctional regulator of mitochondrial energy metabolism with implications across cancer, neurological disease, metabolism, and reproductive biology.