STK11 is a serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members and also functions as a tumor suppressor. It functions in cell metabolism, cell polarity, apoptosis and DNA damage response. It is a key upstream regulator of AMPK, mediating the phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2. It thereby regulates the inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. It also modulates cellular polarity by remodeling the actin cytoskeleton. STK11 is required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. It is also involved in DNA damage response via p53/TP53 and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. In vein endothelial cells, STK11 inhibits PI3K/Akt signaling activity and thus induces apoptosis in response to the oxidant peroxynitrite in vitro. In immunohistochemistry of normal tissue, STK11 has moderate cytoplasmic positivity in all tissues throughout the body. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804;