Krüppel-like factor 6 (KLF6)

Krüppel-like factor 6 (KLF6) is a zinc finger transcription factor belonging to the Krüppel-like factor family, characterized by three C-terminal Cys2His2 zinc finger domains that bind GC-rich DNA motifs to regulate gene expression.[1][2][4][9][12] It functions in diverse processes including cell proliferation, differentiation, apoptosis, mitochondrial maintenance, and response to tissue injury, often acting as a tumor suppressor by upregulating genes like p21 and E-cadherin while inhibiting oncogenes.[3][5][11][13] In the kidney, KLF6 is expressed in podocytes and proximal tubules, where its loss protects against acute kidney injury and fibrosis by preserving branched-chain amino acid catabolism and mitochondrial function, whereas overexpression worsens damage.[1][2] Dysregulation, including mutations or splice variants like oncogenic KLF6-SV1, contributes to cancers (e.g., prostate, glioblastoma), glomerulosclerosis, and inflammation-driven diseases.[3][7][11] KLF6 responds early to stressors like TGF-β or toxins, mediating repair but with context-dependent pro-fibrotic roles in liver, heart, and kidney.[1][7][13] No approved drugs directly target KLF6, though its modulation shows preclinical promise for kidney protection and oncology.[1][11]

Other names

Kruppel-like factor 6KLF6-SV1 (splice variant 1, oncogenic isoform)