CAB39L (calcium binding protein 39 like) functions as a critical regulator of cellular metabolism and tumor suppression through activation of the LKB1-AMPK signaling pathway. CAB39L forms a stabilizing complex with LKB1 and CAB39/MO25, which is required for LKB1 kinase activation 1. Once activated, this complex phosphorylates and activates AMPK, leading to downstream activation of PGC1α and promotion of oxidative phosphorylation over glycolysis 1. This mechanism elicits an anti-Warburg effect, shifting cellular metabolism away from the glycolytic phenotype characteristic of cancer cells 1. CAB39L expression is frequently silenced by promoter hypermethylation in multiple cancer types, including gastric cancer, kidney renal clear cell carcinoma, and bladder cancer 123. Loss of CAB39L contributes to carcinogenesis by dysregulating cellular differentiation programs and metabolic homeostasis 3. Clinically, CAB39L serves as both a diagnostic and prognostic biomarker, with higher expression levels associated with improved patient survival outcomes in hepatocellular carcinoma and kidney cancer 42. The protein also shows genetic associations with neuropathic pain susceptibility and metabolic traits like fat distribution 56.