KLF16 is a zinc finger transcription factor that exhibits context-dependent functions across different tissues and disease states. In hepatic metabolism, KLF16 acts as a protective factor by directly binding to and activating the PPARα promoter, enhancing fatty acid oxidation and improving hepatic steatosis and insulin resistance 1. However, KLF16 predominantly functions as an oncogene in multiple cancer types. In bladder cancer, KLF16 forms a positive feedback loop with MYC, creating nuclear condensates that enhance MYC's transcriptional activity while simultaneously competing with DUSP16 mRNA for WBP11 binding, leading to ERK1/2 activation and MYC protein stabilization 2. KLF16 also promotes bladder cancer progression by directly binding to the TGFBR3 promoter and suppressing this tumor suppressor gene 3. In glioma, KLF16 suppresses cell proliferation by targeting TFAM 4, while in lung adenocarcinoma and osteosarcoma, it promotes cancer progression by upregulating LMNB2 and GPX8, respectively 56. Additionally, KLF16 postzygotic mutations contribute to autism spectrum disorder risk 7. These findings highlight KLF16's dual role as both a metabolic regulator and cancer-associated transcription factor.